Author: "Arias, Maykel" - Searchworks@Jio Institute Digital Library Search Results

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256 results on '"Arias, Maykel"'

1. The importance of murine phospho-MLKL-S345 in situ detection for necroptosis assessment in vivo

Author: Kelepouras, Konstantinos, Saggau, Julia, Varanda, Ana Beatriz, Zrilic, Matea, Kiefer, Christine, Rakhsh-Khorshid, Hassan, Lisewski, Ina, Uranga-Murillo, Iratxe, Arias, Maykel, Pardo, Julian, Tonnus, Wulf, Linkermann, Andreas, Annibaldi, Alessandro, Walczak, Henning, and Liccardi, Gianmaria
Published: 2024
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2. Fungal polysaccharides from Inonotus obliquus are agonists for Toll-like receptors and induce macrophage anti-cancer activity

Author: Wold, Christian Winther, Christopoulos, Panagiotis F., Arias, Maykel A., Dzovor, Deborah Elikplim, Øynebråten, Inger, Corthay, Alexandre, and Inngjerdingen, Kari Tvete
Published: 2024
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3. Identification of FasL as a crucial host factor driving COVID-19 pathology and lethality

Author: Albert, Marie-Christine, Uranga-Murillo, Iratxe, Arias, Maykel, De Miguel, Diego, Peña, Natacha, Montinaro, Antonella, Varanda, Ana Beatriz, Theobald, Sebastian J., Areso, Itziar, Saggau, Julia, Koch, Manuel, Liccardi, Gianmaria, Peltzer, Nieves, Rybniker, Jan, Hurtado-Guerrero, Ramón, Merino, Pedro, Monzón, Marta, Badiola, Juan J., Reindl-Schwaighofer, Roman, Sanz-Pamplona, Rebeca, Cebollada-Solanas, Alberto, Megyesfalvi, Zsolt, Dome, Balazs, Secrier, Maria, Hartmann, Boris, Bergmann, Michael, Pardo, Julián, and Walczak, Henning
Published: 2024
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4. Seroprevalence of anti-SARS-CoV-2 antibodies in household domestic ferrets (Mustela putorius furo) in Spain, 2019–2023

Author: Giner, Jacobo, Lebrero, María Eugenia, Trotta, Michele, Rueda, Pablo, Vilalta, Laura, Verde, Maite, Hurtado-Guerrero, Ramón, Pardo, Julián, Lacasta, Delia, Santiago, Llipsy, Arias, Maykel, Peña-Fresneda, Natacha, Montesinos, Andrés, Pérez, María D., Fernández, Antonio, and Villanueva-Saz, Sergio
Published: 2024
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5. Distinct cell death pathways induced by granzymes collectively protect against intestinal Salmonella infection

Author: Chawla, Amanpreet Singh, Vandereyken, Maud, Arias, Maykel, Santiago, Llipsy, Dikovskaya, Dina, Nguyen, Chi, Skariah, Neema, Wenner, Nicolas, Golovchenko, Natasha B., Thomson, Sarah J., Ondari, Edna, Garzón-Tituaña, Marcela, Anderson, Christopher J., Bergkessel, Megan, C. D. Hinton, Jay, Edelblum, Karen L., Pardo, Julian, and Swamy, Mahima
Published: 2024
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6. The dynamics of neutralizing antibodies against SARS-CoV-2 in cats naturally exposed to virus reveals an increase in antibody activity after re-infection

Author: Villanueva-Saz, Sergio, Martínez, Marivi, Rueda, Pablo, Bolea, Sara, Pérez, María Dolores, Verde, Maite, Yzuel, Andrés, Hurtado-Guerrero, Ramón, Pardo, Julián, Santiago, Llipsy, Fernández, Antonio, and Arias, Maykel
Published: 2023
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7. A cross-sectional serosurvey of SARS-CoV-2 and co-infections in stray cats from the second wave to the sixth wave of COVID-19 outbreaks in Spain

Author: Villanueva-Saz, Sergio, Martínez, Mariví, Giner, Jacobo, González, Ana, Tobajas, Ana Pilar, Pérez, María Dolores, Lira-Navarrete, Erandi, González-Ramírez, Andrés Manuel, Macías-León, Javier, Verde, Maite, Yzuel, Andrés, Hurtado-Guerrero, Ramón, Arias, Maykel, Santiago, Llipsy, Aguiló-Gisbert, Jordi, Ruíz, Héctor, Lacasta, Delia, Marteles, Diana, and Fernández, Antonio
Published: 2023
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8. Intravenous administration of BCG in mice promotes natural killer and T cell-mediated antitumor immunity in the lung

Author: Moreo, Eduardo, Jarit-Cabanillas, Aitor, Robles-Vera, Iñaki, Uranga, Santiago, Guerrero, Claudia, Gómez, Ana Belén, Mata-Martínez, Pablo, Minute, Luna, Araujo-Voces, Miguel, Felgueres, María José, Esteso, Gloria, Uranga-Murillo, Iratxe, Arias, Maykel, Pardo, Julián, Martín, Carlos, Valés-Gómez, Mar, del Fresno, Carlos, Sancho, David, and Aguiló, Nacho
Published: 2023
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9. Ultrastructural analysis and three-dimensional reconstruction of cellular structures involved in SARS-CoV-2 spread

Author: Baselga, Marta, Moreo, Eduardo, Uranga-Murillo, Iratxe, Arias, Maykel, and Junquera, Concepción
Published: 2023
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10. Selective detection of active extracellular granzyme A by using a novel fluorescent immunoprobe with application to inflammatory diseases

Author: Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Gobierno de Aragón, Agencia Estatal de Investigación (España), European Research Council, Ministerio de Economía y Competitividad (España), Senán Salinas, Ana [0009-0009-5597-851X], Comas, Laura [0000-0002-3843-1231], Esteban, Patricia [0000-0003-4123-3524], Garzón, Marcela [0000-0001-6778-0636], Santiago, Llipsy [0000-0002-1861-5981], Domingo, María Pilar [0000-0002-6829-8769], Ramírez-Labrada, Ariel [0000-0002-3888-7036], Paño, José Ramón [0000-0002-9600-8116], Vendrell, Marc [0000-0002-5392-9740], Pardo, Julián [0000-0003-0154-0730], Arias, Maykel [0000-0002-9730-2210], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Gálvez Buerba, Eva Mª [eva@icb.csic.es], Arias, Maykel [maykelariascabrero@gmail.com], Senán Salinas, Ana, Comas, Laura, Esteban, Patricia, Garzón, Marcela, Cheng, Zhiming, Santiago, Llipsy, Domingo, María Pilar, Ramírez-Labrada, Ariel, Paño, José Ramón, Vendrell, Marc, Pardo, Julián, Arias, Maykel, Gálvez Buerba, Eva Mª, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Gobierno de Aragón, Agencia Estatal de Investigación (España), European Research Council, Ministerio de Economía y Competitividad (España), Senán Salinas, Ana [0009-0009-5597-851X], Comas, Laura [0000-0002-3843-1231], Esteban, Patricia [0000-0003-4123-3524], Garzón, Marcela [0000-0001-6778-0636], Santiago, Llipsy [0000-0002-1861-5981], Domingo, María Pilar [0000-0002-6829-8769], Ramírez-Labrada, Ariel [0000-0002-3888-7036], Paño, José Ramón [0000-0002-9600-8116], Vendrell, Marc [0000-0002-5392-9740], Pardo, Julián [0000-0003-0154-0730], Arias, Maykel [0000-0002-9730-2210], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Gálvez Buerba, Eva Mª [eva@icb.csic.es], Arias, Maykel [maykelariascabrero@gmail.com], Senán Salinas, Ana, Comas, Laura, Esteban, Patricia, Garzón, Marcela, Cheng, Zhiming, Santiago, Llipsy, Domingo, María Pilar, Ramírez-Labrada, Ariel, Paño, José Ramón, Vendrell, Marc, Pardo, Julián, Arias, Maykel, and Gálvez Buerba, Eva Mª
Abstract: Granzymes (Gzms), a family of serine proteases, expressed by immune and nonimmune cells, present perforin-dependent and independent intracellular and extracellular functions. When released in the extracellular space, GzmA, with trypsin-like activity, is involved in the pathophysiology of different inflammatory diseases. However, there are no validated specific systems to detect active forms of extracellular GzmA, making it difficult to assess its biological relevance and potential use as a biomarker. Here, we have developed fluorescence-energy resonance-transfer (FRET)-based peptide probes (FAM-peptide-DABCYL) to specifically detect GzmA activity in tissue samples and biological fluids in both mouse and human samples during inflammatory diseases. An initial probe was developed and incubated with GzmA and different proteases like GzmB and others with similar cleavage specificity as GzmA like GzmK, thrombin, trypsin, kallikrein, or plasmin. After measuring fluorescence, the probe showed very good specificity and sensitivity for human and mouse GzmA when compared to GzmB, its closest homologue GzmK, and with thrombin. The specificity of this probe was further refined by incubating the samples in a coated plate with a GzmA-specific antibody before adding the probe. The results show a high specific detection of soluble GzmA even when compared with other soluble proteases with very similar cleavage specificity like thrombin, GzmK, trypsin, kallikrein, or plasmin, which shows nearly no fluorescence signal. The high specific detection of GzmA was validated, showing that using pure proteins and serum and tissue samples from GzmA-deficient mice presented a significant reduction in the signal compared with WT mice. The utility of this system in humans was confirmed, showing that GzmA activity was significantly higher in serum samples from septic patients in comparison with healthy donors. Our results present a new immunoprobe with utility to detect extracellular GzmA activity
Published: 2024

11. Supporting information for Selective detection of active extracellular granzyme A by using a novel fluorescent immunoprobe with application to inflammatory diseases [Dataset]

Author: Senán Salinas, Ana [0009-0009-5597-851X], Comas, Laura [0000-0002-3843-1231], Esteban, Patricia [0000-0003-4123-3524], Garzón, Marcela [0000-0001-6778-0636], Santiago, Llipsy [0000-0002-1861-5981], Domingo, María Pilar [0000-0002-6829-8769], Ramírez-Labrada, Ariel [0000-0002-3888-7036], Paño, José Ramón [0000-0002-9600-8116], Vendrell, Marc [0000-0002-5392-9740], Pardo, Julián [0000-0003-0154-0730], Arias, Maykel [0000-0002-9730-2210], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Gálvez Buerba, Eva Mª [eva@icb.csic.es], Arias, Maykel [maykelariascabrero@gmail.com], Senán Salinas, Ana, Comas, Laura, Esteban, Patricia, Garzón, Marcela, Santiago, Llipsy, Domingo, María Pilar, Ramírez-Labrada, Ariel, Paño, José Ramón, Vendrell, Marc, Pardo, Julián, Arias, Maykel, Gálvez Buerba, Eva Mª, Senán Salinas, Ana [0009-0009-5597-851X], Comas, Laura [0000-0002-3843-1231], Esteban, Patricia [0000-0003-4123-3524], Garzón, Marcela [0000-0001-6778-0636], Santiago, Llipsy [0000-0002-1861-5981], Domingo, María Pilar [0000-0002-6829-8769], Ramírez-Labrada, Ariel [0000-0002-3888-7036], Paño, José Ramón [0000-0002-9600-8116], Vendrell, Marc [0000-0002-5392-9740], Pardo, Julián [0000-0003-0154-0730], Arias, Maykel [0000-0002-9730-2210], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Gálvez Buerba, Eva Mª [eva@icb.csic.es], Arias, Maykel [maykelariascabrero@gmail.com], Senán Salinas, Ana, Comas, Laura, Esteban, Patricia, Garzón, Marcela, Santiago, Llipsy, Domingo, María Pilar, Ramírez-Labrada, Ariel, Paño, José Ramón, Vendrell, Marc, Pardo, Julián, Arias, Maykel, and Gálvez Buerba, Eva Mª
Abstract: Supplementary table 1. Concentration of trypsin-like proteases presenting similar enzyme activity using a common substrate.-- The substrate Nɑ-CBZ-L-Lysine thiobenzyl ester hydrochloride was incubated with hGzmA (66.7 nM), hGzmK (2.4 nM), mGzmA (4 nm), Kallikrein (3.7 nM), Plasmin (4.3 nM) and Trypsin (0.4 nM) for 30 min as described in methods. The absorbance was measured. The values obtained at each time were subtracted from the substrate signal in the absence of enzymes. Data represent the mean of three independent replicates.
Published: 2024

12. Multiparametric in vitro and in vivo analysis of the safety profile of self-assembling peptides

Author: Istituto Nazionale per l'Assicurazione Contro Gli Infortuni sul Lavoro, Ministero della Salute, Governo Italiano, Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (España), Instituto de Salud Carlos III, European Commission, Gobierno de Aragón, Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Aspanoa, Asociación Carrera de la Mujer Ciudad de Monzón, Universidad de Zaragoza, Banco Santander, Asociación Española Contra el Cáncer, Fundación Científica Asociación Española Contra el Cáncer, Ramírez-Labrada, Ariel [0000-0002-3888-7036], Santiago, Llipsy [0000-0002-1861-5981], Pesini, Cecilia [0000-0002-8707-2722], Arias, Maykel [0000-0002-9730-2210], Ciulla, Maria Gessica [0000-0001-8738-1712], Forouharshad, Mahdi [0000-0002-6139-9110], Pardo, Julián [0000-0003-0154-0730], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Gelain, Fabrizio [0000-0002-2624-5853], Ramírez-Labrada, Ariel, Santiago, Llipsy, Pesini, Cecilia, Arrieta, Marta, Arias, Maykel, Calvo Pérez, Adanys, Ciulla, Maria Gessica, Forouharshad, Mahdi, Pardo, Julián, Gálvez Buerba, Eva Mª, Gelain, Fabrizio, Istituto Nazionale per l'Assicurazione Contro Gli Infortuni sul Lavoro, Ministero della Salute, Governo Italiano, Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (España), Instituto de Salud Carlos III, European Commission, Gobierno de Aragón, Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Aspanoa, Asociación Carrera de la Mujer Ciudad de Monzón, Universidad de Zaragoza, Banco Santander, Asociación Española Contra el Cáncer, Fundación Científica Asociación Española Contra el Cáncer, Ramírez-Labrada, Ariel [0000-0002-3888-7036], Santiago, Llipsy [0000-0002-1861-5981], Pesini, Cecilia [0000-0002-8707-2722], Arias, Maykel [0000-0002-9730-2210], Ciulla, Maria Gessica [0000-0001-8738-1712], Forouharshad, Mahdi [0000-0002-6139-9110], Pardo, Julián [0000-0003-0154-0730], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Gelain, Fabrizio [0000-0002-2624-5853], Ramírez-Labrada, Ariel, Santiago, Llipsy, Pesini, Cecilia, Arrieta, Marta, Arias, Maykel, Calvo Pérez, Adanys, Ciulla, Maria Gessica, Forouharshad, Mahdi, Pardo, Julián, Gálvez Buerba, Eva Mª, and Gelain, Fabrizio
Abstract: Self-assembling peptides (SAPs) have gained significant attention in biomedicine because of their unique properties and ability to undergo molecular self-assembly driven by non-covalent interactions. By manipulating their composition and structure, SAPs can form well-ordered nanostructures with enhanced selectivity, stability and biocompatibility. SAPs offer advantages such as high chemical and biological diversity and the potential for functionalization. However, studies concerning its potentially toxic effects are very scarce, a limitation that compromises its potential translation to humans. This study investigates the potentially toxic effects of six different SAP formulations composed of natural amino acids designed for nervous tissue engineering and amenable to ready cross-linking boosting their biomechanical properties. All methods were performed in accordance with the relevant guidelines and regulations. A wound-healing assay was performed to evaluate how SAPs modify cell migration. The results in vitro demonstrated that SAPs did not induce genotoxicity neither skin sensitization. In vivo, SAPs were well-tolerated without any signs of acute systemic toxicity. Interestingly, SAPs were found to promote the migration of endothelial, macrophage, fibroblast, and neuronal-like cells in vitro, supporting a high potential for tissue regeneration. These findings contribute to the development and translation of SAP-based biomaterials for biomedical applications.
Published: 2024

13. CAR Immunotherapy for the treatment of infectious diseases: a systematic review

Author: Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (España), Instituto de Salud Carlos III, European Commission, Gobierno de Aragón, Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Aspanoa, Asociación Carrera de la Mujer Ciudad de Monzón, Universidad de Zaragoza, Banco Santander, Asociación Española Contra el Cáncer, Morte Romea, Elena [0000-0001-9262-2461], Pesini, Cecilia [0000-0002-8707-2722], Pellejero, Galadriel [0000-0002-2728-5435], Martínez Lostao, Luis [0000-0003-3043-147X], Toyas, Carla [0000-0002-4217-6317], Redrado, Sergio [0000-0002-8404-0012], Dolader, Elena [0009-0007-5333-4214], Arias, Maykel [0000-0002-9730-2210], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Sanz-Pamplona, Rebeca [0000-0002-2187-3527], Pardo, Julián [0000-0003-0154-0730], Paño, José Ramón [0000-0002-9600-8116], Ramírez-Labrada, Ariel [0000-0002-3888-7036], Ramírez-Labrada, Ariel [aramirezlabrada@yahoo.es], Morte Romea, Elena, Pesini, Cecilia, Pellejero, Galadriel, Martínez-Lostao, Luis, Loscos, Silvia, Toyas, Carla, Redrado, Sergio, Dolader, Elena, Arias, Maykel, Gálvez Buerba, Eva Mª, Sanz-Pamplona, Rebeca, Pardo, Julián, Paño, José Ramón, Ramírez-Labrada, Ariel, Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (España), Instituto de Salud Carlos III, European Commission, Gobierno de Aragón, Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Aspanoa, Asociación Carrera de la Mujer Ciudad de Monzón, Universidad de Zaragoza, Banco Santander, Asociación Española Contra el Cáncer, Morte Romea, Elena [0000-0001-9262-2461], Pesini, Cecilia [0000-0002-8707-2722], Pellejero, Galadriel [0000-0002-2728-5435], Martínez Lostao, Luis [0000-0003-3043-147X], Toyas, Carla [0000-0002-4217-6317], Redrado, Sergio [0000-0002-8404-0012], Dolader, Elena [0009-0007-5333-4214], Arias, Maykel [0000-0002-9730-2210], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Sanz-Pamplona, Rebeca [0000-0002-2187-3527], Pardo, Julián [0000-0003-0154-0730], Paño, José Ramón [0000-0002-9600-8116], Ramírez-Labrada, Ariel [0000-0002-3888-7036], Ramírez-Labrada, Ariel [aramirezlabrada@yahoo.es], Morte Romea, Elena, Pesini, Cecilia, Pellejero, Galadriel, Martínez-Lostao, Luis, Loscos, Silvia, Toyas, Carla, Redrado, Sergio, Dolader, Elena, Arias, Maykel, Gálvez Buerba, Eva Mª, Sanz-Pamplona, Rebeca, Pardo, Julián, Paño, José Ramón, and Ramírez-Labrada, Ariel
Abstract: Immunotherapy treatments aim to modulate the host’s immune response to either mitigate it in inflammatory/autoimmune disease or enhance it against infection or cancer. Among different immunotherapies reaching clinical application during the last years, chimeric antigen receptor (CAR) immunotherapy has emerged as an effective treatment for cancer where different CAR T cells have already been approved. Yet their use against infectious diseases is an area still relatively poorly explored, albeit with tremendous potential for research and clinical application. Infectious diseases represent a global health challenge, with the escalating threat of antimicrobial resistance underscoring the need for alternative therapeutic approaches. This review aims to systematically evaluate the current applications of CAR immunotherapy in infectious diseases and discuss its potential for future applications. Notably, CAR cell therapies, initially developed for cancer treatment, are gaining recognition as potential remedies for infectious diseases. The review sheds light on significant progress in CAR T cell therapy directed at viral and opportunistic fungal infections.
Published: 2024

14. Nanobody based immunotherapy for the treatment of invasive fungal infections

Author: Gobierno de Aragón, European Commission, Agencia Estatal de Investigación (España), Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (España), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Redrado, Sergio [0000-0002-8404-0012], Dolader, Elena [0009-0007-5333-4214], Macías León, Javier [0000-0001-6815-6720], Domingo, María Pilar [0000-0002-6829-8769], Esteban, Patricia [0000-0003-4123-3524], Arias, Maykel [0000-0002-9730-2210], Ramírez-Labrada, Ariel [0000-0002-3888-7036], Pardo, Julián [0000-0003-0154-0730], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Sánchez-Martínez, Diego, Redrado, Sergio, Dolader, Elena, Macías León, Javier, Domingo, María Pilar, Esteban, Patricia, Arias, Maykel, Ramírez-Labrada, Ariel, Hurtado-Guerrero, R., Pardo, Julián, Gálvez Buerba, Eva Mª, Gobierno de Aragón, European Commission, Agencia Estatal de Investigación (España), Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (España), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Redrado, Sergio [0000-0002-8404-0012], Dolader, Elena [0009-0007-5333-4214], Macías León, Javier [0000-0001-6815-6720], Domingo, María Pilar [0000-0002-6829-8769], Esteban, Patricia [0000-0003-4123-3524], Arias, Maykel [0000-0002-9730-2210], Ramírez-Labrada, Ariel [0000-0002-3888-7036], Pardo, Julián [0000-0003-0154-0730], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Sánchez-Martínez, Diego, Redrado, Sergio, Dolader, Elena, Macías León, Javier, Domingo, María Pilar, Esteban, Patricia, Arias, Maykel, Ramírez-Labrada, Ariel, Hurtado-Guerrero, R., Pardo, Julián, and Gálvez Buerba, Eva Mª
Abstract: The invasive fungal infections ratios of mortality are between 25% and 70% depending on the type of microorganism and the population at risk, affecting mostly immunocompromised patients. Aspergillus spp. and Cryptococcus spp. are two of the main responsible for these infections. The late non-specific diagnosis and the increasing resistance of the strains highlight the importance of finding new therapeutic alternatives.
Published: 2024

15. Broad protection against invasive fungal disease from a nanobody targeting the active site of fungal b‐1,3‐glucanosyltransferases

Author: Redrado-Hernández, Sergio, primary, Macías-León, Javier, additional, Castro-López, Jorge, additional, Sanz, Ana Belén, additional, Dolader, Elena, additional, Arias, Maykel, additional, González-Ramírez, Andrés Manuel, additional, Sánchez-Navarro, David, additional, Petryk, Yuliya, additional, Farkaš, Vladimir, additional, Vincke, Cecile, additional, Muyldermans, Serge, additional, García-Barbazán, Irene, additional, Del Agua, Celia, additional, Zaragoza, oscar, additional, Arroyo, Javier, additional, Pardo, Julián, additional, Gálvez, Eva, additional, and Hurtado-Guerrero, Ramon, additional
Published: 2024
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16. Identification of FasL as a crucial host factor driving COVID-19 pathology and lethality

Author: Albert, Marie Christine, Uranga-Murillo, Iratxe, Arias, Maykel, De Miguel, Diego, Peña, Natacha, Montinaro, Antonella, Varanda, Ana Beatriz, Theobald, Sebastian J., Areso, Itziar, Saggau, Julia, Koch, Manuel, Liccardi, Gianmaria, Peltzer, Nieves, Rybniker, Jan, Hurtado-Guerrero, Ramón, Merino, Pedro, Monzón, Marta, Badiola, Juan J., Reindl-Schwaighofer, Roman, Sanz-Pamplona, Rebeca, Cebollada-Solanas, Alberto, Megyesfalvi, Zsolt, Dome, Balazs, Secrier, Maria, Hartmann, Boris, Bergmann, Michael, Pardo, Julián, Walczak, Henning, Albert, Marie Christine, Uranga-Murillo, Iratxe, Arias, Maykel, De Miguel, Diego, Peña, Natacha, Montinaro, Antonella, Varanda, Ana Beatriz, Theobald, Sebastian J., Areso, Itziar, Saggau, Julia, Koch, Manuel, Liccardi, Gianmaria, Peltzer, Nieves, Rybniker, Jan, Hurtado-Guerrero, Ramón, Merino, Pedro, Monzón, Marta, Badiola, Juan J., Reindl-Schwaighofer, Roman, Sanz-Pamplona, Rebeca, Cebollada-Solanas, Alberto, Megyesfalvi, Zsolt, Dome, Balazs, Secrier, Maria, Hartmann, Boris, Bergmann, Michael, Pardo, Julián, and Walczak, Henning
Abstract: The dysregulated immune response and inflammation resulting in severe COVID-19 are still incompletely understood. Having recently determined that aberrant death-ligand-induced cell death can cause lethal inflammation, we hypothesized that this process might also cause or contribute to inflammatory disease and lung failure following SARS-CoV-2 infection. To test this hypothesis, we developed a novel mouse-adapted SARS-CoV-2 model (MA20) that recapitulates key pathological features of COVID-19. Concomitantly with occurrence of cell death and inflammation, FasL expression was significantly increased on inflammatory monocytic macrophages and NK cells in the lungs of MA20-infected mice. Importantly, therapeutic FasL inhibition markedly increased survival of both, young and old MA20-infected mice coincident with substantially reduced cell death and inflammation in their lungs. Intriguingly, FasL was also increased in the bronchoalveolar lavage fluid of critically-ill COVID-19 patients. Together, these results identify FasL as a crucial host factor driving the immuno-pathology that underlies COVID-19 severity and lethality, and imply that patients with severe COVID-19 may significantly benefit from therapeutic inhibition of FasL., The dysregulated immune response and inflammation resulting in severe COVID-19 are still incompletely understood. Having recently determined that aberrant death-ligand-induced cell death can cause lethal inflammation, we hypothesized that this process might also cause or contribute to inflammatory disease and lung failure following SARS-CoV-2 infection. To test this hypothesis, we developed a novel mouse-adapted SARS-CoV-2 model (MA20) that recapitulates key pathological features of COVID-19. Concomitantly with occurrence of cell death and inflammation, FasL expression was significantly increased on inflammatory monocytic macrophages and NK cells in the lungs of MA20-infected mice. Importantly, therapeutic FasL inhibition markedly increased survival of both, young and old MA20-infected mice coincident with substantially reduced cell death and inflammation in their lungs. Intriguingly, FasL was also increased in the bronchoalveolar lavage fluid of critically-ill COVID-19 patients. Together, these results identify FasL as a crucial host factor driving the immuno-pathology that underlies COVID-19 severity and lethality, and imply that patients with severe COVID-19 may significantly benefit from therapeutic inhibition of FasL.
Published: 2024

17. Broad Protection against Invasive Fungal Disease from a Nanobody Targeting the Active Site of Fungal β‐1,3‐Glucanosyltransferases.

Author: Redrado‐Hernández, Sergio, Macías‐León, Javier, Castro‐López, Jorge, Belén Sanz, Ana, Dolader, Elena, Arias, Maykel, González‐Ramírez, Andrés Manuel, Sánchez‐Navarro, David, Petryk, Yuliya, Farkaš, Vladimír, Vincke, Cécile, Muyldermans, Serge, García‐Barbazán, Irene, del Agua, Celia, Zaragoza, Oscar, Arroyo, Javier, Pardo, Julián, Gálvez, Eva M., and Hurtado‐Guerrero, Ramon
Subjects: FUNGAL cell walls, FUNGAL enzymes, MYCOSES, ASPERGILLUS fumigatus, CRYPTOCOCCUS neoformans
Abstract: Invasive fungal disease accounts for about 3.8 million deaths annually, an unacceptable rate that urgently prompts the discovery of new knowledge‐driven treatments. We report the use of camelid single‐domain nanobodies (Nbs) against fungal β‐1,3‐glucanosyltransferases (Gel) involved in β‐1,3‐glucan transglycosylation. Crystal structures of two Nbs with Gel4 from Aspergillus fumigatus revealed binding to a dissimilar CBM43 domain and a highly conserved catalytic domain across fungal species, respectively. Anti‐Gel4 active site Nb3 showed significant antifungal efficacy in vitro and in vivo prophylactically and therapeutically against different A. fumigatus and Cryptococcus neoformans isolates, reducing the fungal burden and disease severity, thus significantly improving immunocompromised animal survival. Notably, C. deneoformans (serotype D) strains were more susceptible to Nb3 and genetic Gel deletion than C. neoformans (serotype A) strains, indicating a key role for β‐1,3‐glucan remodelling in C. deneoformans survival. These findings add new insight about the role of β‐1,3‐glucan in fungal biology and demonstrate the potential of nanobodies in targeting fungal enzymes to combat invasive fungal diseases. [ABSTRACT FROM AUTHOR]
Published: 2024
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18. The Influence of Lung Microbiota on Lung Carcinogenesis, Immunity, and Immunotherapy

Author: Ramírez-Labrada, Ariel G., Isla, Dolores, Artal, Angel, Arias, Maykel, Rezusta, Antonio, Pardo, Julián, and Gálvez, Eva M.
Published: 2020
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19. CAR Immunotherapy for the treatment of infectious diseases: a systematic review

Author: Morte-Romea, Elena, primary, Pesini, Cecilia, additional, Pellejero-Sagastizábal, Galadriel, additional, Letona-Giménez, Santiago, additional, Martínez-Lostao, Luis, additional, Aranda, Silvia Loscos, additional, Toyas, Carla, additional, Redrado, Sergio, additional, Dolader-Ballesteros, Elena, additional, Arias, Maykel, additional, Galvez, Eva M., additional, Sanz-Pamplona, Rebeca, additional, Pardo, Julián, additional, Paño-Pardo, Jose Ramón, additional, and Ramírez-Labrada, Ariel, additional
Published: 2024
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20. The dynamics of neutralizing antibodies against SARS-CoV-2 in cats naturally exposed to virus reveals an increase in antibody activity after re-infection

Author: ARAID Foundation, Ministerio de Ciencia, Innovación y Universidades (España), Gobierno de Aragón, European Commission, Instituto de Salud Carlos III, Fundación Banco Santander, Universidad de Zaragoza, Agencia Estatal de Investigación (España), Villanueva-Saz, Sergio [0000-0001-6209-4282], Pardo, Julián [0000-0003-0154-0730], Santiago, Llipsy [0000-0002-1861-5981], Fernández Casanovas, Antonio [0000-0002-2557-4890], Arias, Maykel [0000-0002-9730-2210], Villanueva-Saz, Sergio, Martínez, Mariví, Rueda, Pablo, Bolea, Sara, Pérez, María Dolores, Verde, Maite, Yzuel, Andrés, Hurtado-Guerrero, R., Pardo, Julián, Santiago, Llipsy, Fernández Casanovas, Antonio, Arias, Maykel, ARAID Foundation, Ministerio de Ciencia, Innovación y Universidades (España), Gobierno de Aragón, European Commission, Instituto de Salud Carlos III, Fundación Banco Santander, Universidad de Zaragoza, Agencia Estatal de Investigación (España), Villanueva-Saz, Sergio [0000-0001-6209-4282], Pardo, Julián [0000-0003-0154-0730], Santiago, Llipsy [0000-0002-1861-5981], Fernández Casanovas, Antonio [0000-0002-2557-4890], Arias, Maykel [0000-0002-9730-2210], Villanueva-Saz, Sergio, Martínez, Mariví, Rueda, Pablo, Bolea, Sara, Pérez, María Dolores, Verde, Maite, Yzuel, Andrés, Hurtado-Guerrero, R., Pardo, Julián, Santiago, Llipsy, Fernández Casanovas, Antonio, and Arias, Maykel
Abstract: Severe Acute Respiratory Syndrome Coronavirus 2 is the causative agent of Coronavirus Disease 2019 in humans. To date, little is known about the persistence of antibodies against SARS-CoV-2 in animals under natural conditions, in particular susceptible pets such as cat. This study reports the detection and monitoring of the humoral response against SARS-CoV-2 including the detection of immunoglobulins G specific for receptor binding domain of SARS-CoV-2 spike protein by an enzyme-linked immunosorbent assay and neutralizing antibodies by virus neutralization assay. Results showed that these antibodies last longer than 16 months in two naturally apparently healthy infected cats with the absence of clinicopathological findings during the follow-up. Moreover, re-infection is also possible with an important increase in virus neutralization test titers in both animals with no evident systemic signs found during each physical examination and with values of hematologic and biochemical parameters inside the normal reference intervals. Our results confirm a slow but progressive decrease of the kinetics and immunity of neutralizing antibodies in cats after the infection. Furthermore, similar to humans SARS-CoV-2 reinfection can stimulate an increase of the neutralizing antibodies determined by these two serological techniques in domestic cats.
Published: 2023

21. Identification of an ASC oligomerization inhibitor for the treatment of inflammatory diseases

Author: Soriano-Teruel, Paula M., García‑Laínez, Guillermo, Marco-Salvador, María, Pardo, Julián, Arias, Maykel, DeFord, Christian, Merfort, Irmgard, Vicent, María J., Pelegrín, Pablo, Sancho, Mónica, and Orzáez, Mar
Published: 2021
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22. Serological exposure to influenza A in cats from an area with wild birds positive for avian influenza.

Author: Villanueva‐Saz, Sergio, Martínez, Mariví, Rueda, Pablo, Pérez, María Dolores, Lacasta, Delia, Marteles, Diana, Ruíz, Héctor, Gonzalez, Ana, Verde, María Teresa, Pardo, Julián, Arias, Maykel, Peña‐Fresneda, Natacha, Fernández, Antonio, and Trotta, Michele
Subjects: AVIAN influenza, INFLUENZA, CAT diseases, FERAL cats, ENZYME-linked immunosorbent assay, CATS, INFLUENZA viruses
Abstract: Influenza A is an emerging zoonotic virus with worldwide distribution. To our knowledge, no studies have been conducted to assess influenza A exposure in stray cats in regions with positive cases of wild birds. This study aimed to determine the seroprevalence of anti‐influenza A antibodies in feral cats from a region in Spain with cases of positive wild birds. A cross‐sectional study of stray cats (n = 183) was conducted between March 2022 and March 2023. The presence of antibodies against the influenza A virus was tested using a commercial enzyme‐linked immunosorbent assay kit adapted for this study and confirmed by competitive enzyme‐linked immunosorbent assay for the detection of antibodies against the haemagglutinin H5. During sample collection, none of the cats exhibited clinical signs of illness. Four of the 183 animals tested showed anti‐influenza A antibodies by ELISA, and the seroprevalence of influenza A was 2.19% (95% confidence interval 0.85%–5.48%). Due to the low number of positive cases detected, it appears that cats did not have an important epidemiological role in influenza A transmission during this period. [ABSTRACT FROM AUTHOR]
Published: 2024
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23. Serological exposure to influenza A in cats from an area with wild birds positive for avian influenza

Author: Villanueva‐Saz, Sergio, primary, Martínez, Mariví, additional, Rueda, Pablo, additional, Pérez, María Dolores, additional, Lacasta, Delia, additional, Marteles, Diana, additional, Ruíz, Héctor, additional, Gonzalez, Ana, additional, Verde, María Teresa, additional, Pardo, Julián, additional, Arias, Maykel, additional, Peña‐Fresneda, Natacha, additional, Fernández, Antonio, additional, and Trotta, Michele, additional
Published: 2023
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24. Seroprevalence of anti-SARS-CoV-2 antibodies in household domestic ferrets (Mustela putorius furo) in Spain, 2019–2023

Author: Giner, Jacobo, primary, Lebrero, María Eugenia, additional, Trotta, Michele, additional, Rueda, Pablo, additional, Vilalta, Laura, additional, Verde, Maite, additional, Hurtado-Guerrero, Ramón, additional, Pardo, Julián, additional, Lacasta, Delia, additional, Santiago, Llipsy, additional, Arias, Maykel, additional, Peña-Fresneda, Natacha, additional, Montesinos, Andrés, additional, Pérez, María D., additional, Fernández, Antonio, additional, and Villanueva-Saz, Sergio, additional
Published: 2023
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25. The Untold Story of Granzymes in Oncoimmunology: Novel Opportunities with Old Acquaintances

Author: Arias, Maykel, Martínez-Lostao, Luis, Santiago, Llipsy, Ferrandez, Angel, Granville, David J., and Pardo, Julián
Published: 2017
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26. Gut microbiota and systemic inflammation changes after bread consumption: The ingredients and the processing influence

Author: Arias, Maykel, Cobo, Marta, Jaime-Sánchez, Paula, Pastor, Jorge, Marijuan, Pedro, Pardo, Julián, Rezusta, Antonio, and Del Campo, Rosa
Published: 2017
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27. Supplementary material for Integrated analysis of circulating immune cellular and soluble mediators reveals specific COVID19 signatures at hospital admission with utility for prediction of clinical outcomes [Dataset]

Author: European Commission, Gobierno de Aragón, Instituto de Salud Carlos III, Fundación Banco Santander, Universidad de Zaragoza, Agencia Estatal de Investigación (España), Fundación Inocente Inocente, Aspanoa, Asociación Carrera de la Mujer Ciudad de Monzón, Asociación Española Contra el Cáncer, Ministerio de Ciencia, Innovación y Universidades (España), ARAID Foundation, Uranga Murillo, Iratxe [0000-0001-8411-984X], Morte Romea, Elena [0000-0001-9262-2461], Hidalgo, Sandra [0000-0003-1629-9978], Pesini, Cecilia [0000-0002-8707-2722], García-Mulero, Sandra [0000-0003-4931-1267], Sierra Monzón, José L. [0000-0002-8796-2717], Santiago, Llipsy [0000-0002-1861-5981], Arias, Maykel [0000-0002-9730-2210], Miguel, Diego de [0000-0002-8486-8514], Encabo-Berzosa, M. Mar [0000-0001-5533-804X], Gracia Tello, Borja [0000-0003-3248-2908], Sanz-Pamplona, Rebeca [0000-0002-2187-3527], Martínez Lostao, Luis [0000-0003-3043-147X], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Paño, José Ramón [0000-0002-9600-8116], Ramírez-Labrada, Ariel [0000-0002-3888-7036], Pardo, Julián [0000-0003-0154-0730], Paño, José Ramón; Ramírez-Labrada, Ariel; Pardo, Julián, Uranga Murillo, Iratxe, Morte Romea, Elena, Hidalgo, Sandra, Pesini, Cecilia, García-Mulero, Sandra, Sierra Monzón, José L., Santiago, Llipsy, Arias, Maykel, Miguel, Diego de, Encabo-Berzosa, M. Mar, Gracia Tello, Borja, Sanz-Pamplona, Rebeca, Martínez-Lostao, Luis, Gálvez Buerba, Eva Mª, Paño, José Ramón, Ramírez-Labrada, Ariel, Pardo, Julián, European Commission, Gobierno de Aragón, Instituto de Salud Carlos III, Fundación Banco Santander, Universidad de Zaragoza, Agencia Estatal de Investigación (España), Fundación Inocente Inocente, Aspanoa, Asociación Carrera de la Mujer Ciudad de Monzón, Asociación Española Contra el Cáncer, Ministerio de Ciencia, Innovación y Universidades (España), ARAID Foundation, Uranga Murillo, Iratxe [0000-0001-8411-984X], Morte Romea, Elena [0000-0001-9262-2461], Hidalgo, Sandra [0000-0003-1629-9978], Pesini, Cecilia [0000-0002-8707-2722], García-Mulero, Sandra [0000-0003-4931-1267], Sierra Monzón, José L. [0000-0002-8796-2717], Santiago, Llipsy [0000-0002-1861-5981], Arias, Maykel [0000-0002-9730-2210], Miguel, Diego de [0000-0002-8486-8514], Encabo-Berzosa, M. Mar [0000-0001-5533-804X], Gracia Tello, Borja [0000-0003-3248-2908], Sanz-Pamplona, Rebeca [0000-0002-2187-3527], Martínez Lostao, Luis [0000-0003-3043-147X], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Paño, José Ramón [0000-0002-9600-8116], Ramírez-Labrada, Ariel [0000-0002-3888-7036], Pardo, Julián [0000-0003-0154-0730], Paño, José Ramón; Ramírez-Labrada, Ariel; Pardo, Julián, Uranga Murillo, Iratxe, Morte Romea, Elena, Hidalgo, Sandra, Pesini, Cecilia, García-Mulero, Sandra, Sierra Monzón, José L., Santiago, Llipsy, Arias, Maykel, Miguel, Diego de, Encabo-Berzosa, M. Mar, Gracia Tello, Borja, Sanz-Pamplona, Rebeca, Martínez-Lostao, Luis, Gálvez Buerba, Eva Mª, Paño, José Ramón, Ramírez-Labrada, Ariel, and Pardo, Julián
Abstract: Supplementary materials and methods: sample processing, flow cytometry, high dimensional flow cytometry data analysis, multiplex plasma protein analyses, granzyme activity assay in serum, statistics. Supplementary figure legends (1-5). Supplementary table legends (1-7).
Published: 2022

28. Fluorogenic Granzyme A substrates enable real-time imaging of adaptive immune cell activity

Author: Gobierno de Aragón, Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (España), Instituto de Salud Carlos III, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Medical Research Council (UK), Cancer Research UK, European Research Council, Mendive-Tapia, Lorena [0000-0002-3406-5203], Kitamura, Takanori [0000-0003-2032-3918], Samarakoon, Youhani [0000-0002-9845-4232], Roberts, Edward W. [0000-0002-8229-1715], Arias, Maykel [0000-0002-9730-2210], Pardo, Julián [0000-0003-0154-0730], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Cheng, Zhiming, Thompson, Emily J., Mendive-Tapia, Lorena, Scott, Jamie I., Benson, Sam, Kitamura, Takanori, Senán Salinas, Ana, Samarakoon, Youhani, Roberts, Edward W., Arias, Maykel, Pardo, Julián, Gálvez Buerba, Eva Mª, Gobierno de Aragón, Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (España), Instituto de Salud Carlos III, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Medical Research Council (UK), Cancer Research UK, European Research Council, Mendive-Tapia, Lorena [0000-0002-3406-5203], Kitamura, Takanori [0000-0003-2032-3918], Samarakoon, Youhani [0000-0002-9845-4232], Roberts, Edward W. [0000-0002-8229-1715], Arias, Maykel [0000-0002-9730-2210], Pardo, Julián [0000-0003-0154-0730], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Cheng, Zhiming, Thompson, Emily J., Mendive-Tapia, Lorena, Scott, Jamie I., Benson, Sam, Kitamura, Takanori, Senán Salinas, Ana, Samarakoon, Youhani, Roberts, Edward W., Arias, Maykel, Pardo, Julián, and Gálvez Buerba, Eva Mª
Abstract: Cytotoxic immune cells, including T lymphocytes (CTLs) and natural killer (NK) cells, are essential components of the host response against tumors. CTLs and NK cells secrete granzyme A (GzmA) upon recognition of cancer cells; however, there are very few tools that can detect physiological levels of active GzmA with high spatiotemporal resolution. Herein, we report the rational design of the near-infrared fluorogenic substrates for human GzmA and mouse GzmA. These activity-based probes display very high catalytic efficiency and selectivity over other granzymes, as shown in tissue lysates from wild-type and GzmA knock-out mice. Furthermore, we demonstrate that the probes can image how adaptive immune cells respond to antigen-driven recognition of cancer cells in real time.
Published: 2022

29. PD-1 is expressed in cytotoxic granules of NK cells and rapidly mobilized to the cell membrane following recognition of tumor cells

Author: European Commission, Gobierno de Aragón, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Fundación Inocente Inocente, Aspanoa, Asociación Carrera de la Mujer Ciudad de Monzón, ARAID Foundation, Fundación Agencia Aragonesa para la Investigación y el Desarrollo, Fundación Científica Asociación Española Contra el Cáncer, Pesini, Cecilia [0000-0002-8707-2722], Hidalgo, Sandra [0000-0003-1629-9978], Arias, Maykel [0000-0002-9730-2210], Santiago, Llipsy [0000-0002-1861-5981], Calvo, Carlota [0000-0003-1864-4050], Ocáriz, Maitane [0000-0002-7557-7264], Isla, Dolores [0000-0002-2483-198X], Lanuza, Pilar M. [0000-0001-7328-2094], Agustín Ferrández, M. J. [0000-0003-0450-4196], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Ramírez-Labrada, Ariel [0000-0002-3888-7036], Pardo, Julián [0000-0003-0154-0730], Pesini, Cecilia, Hidalgo, Sandra, Arias, Maykel, Santiago, Llipsy, Calvo, Carlota, Ocáriz, Maitane, Isla, Dolores, Lanuza, Pilar M., Agustín Ferrández, M. J., Gálvez Buerba, Eva Mª, Ramírez-Labrada, Ariel, Pardo, Julián, European Commission, Gobierno de Aragón, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Fundación Inocente Inocente, Aspanoa, Asociación Carrera de la Mujer Ciudad de Monzón, ARAID Foundation, Fundación Agencia Aragonesa para la Investigación y el Desarrollo, Fundación Científica Asociación Española Contra el Cáncer, Pesini, Cecilia [0000-0002-8707-2722], Hidalgo, Sandra [0000-0003-1629-9978], Arias, Maykel [0000-0002-9730-2210], Santiago, Llipsy [0000-0002-1861-5981], Calvo, Carlota [0000-0003-1864-4050], Ocáriz, Maitane [0000-0002-7557-7264], Isla, Dolores [0000-0002-2483-198X], Lanuza, Pilar M. [0000-0001-7328-2094], Agustín Ferrández, M. J. [0000-0003-0450-4196], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Ramírez-Labrada, Ariel [0000-0002-3888-7036], Pardo, Julián [0000-0003-0154-0730], Pesini, Cecilia, Hidalgo, Sandra, Arias, Maykel, Santiago, Llipsy, Calvo, Carlota, Ocáriz, Maitane, Isla, Dolores, Lanuza, Pilar M., Agustín Ferrández, M. J., Gálvez Buerba, Eva Mª, Ramírez-Labrada, Ariel, and Pardo, Julián
Abstract: The contribution of the T cell-related inhibitory checkpoint PD-1 to the regulation of NK cell activity is still not clear with contradictory results concerning its expression and role in the modulation of NK cell cytotoxicity. We provide novel key findings on the mechanism involved in the regulation of PD-1 expression on NK cell membrane and its functional consequences for the elimination of cancer cells. In contrast to freshly isolated NK cells from cancer patients, those from healthy donors did not express PD-1 on the cell membrane. However, when healthy NK cells were incubated with tumor target cells, membrane PD-1 expression increased, concurrent with the CD107a surface mobilization. This finding suggested that PD-1 was translocated to the cell membrane during NK cell degranulation after contact with target cells. Indeed, cytosolic PD-1 was expressed in freshly-isolated-NK cells and partly co-localized with CD107a and GzmB, confirming that membrane PD-1 corresponded to a pool of preformed PD-1. Moreover, NK cells that had mobilized PD-1 to the cell membrane presented a significantly reduced antitumor activity on PD-L1-expressing-tumor cells in vitro and in vivo, which was partly reversed by using anti-PD-1 blocking antibodies. Our results indicate that NK cells from healthy individuals express cytotoxic granule-associated PD-1, which is rapidly mobilized to the cell membrane after interaction with tumor target cells. This novel finding helps to understand how PD-1 expression is regulated on NK cell membrane and the functional consequences of this expression during the elimination of tumor cells, which will help to design more efficient NK cell-based cancer immunotherapies.
Published: 2022

30. All about (NK cell-mediated) death in two acts and an unexpected encore: initiation, execution and activation of adaptive immunity

Author: Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), European Commission, Gobierno de Aragón, Agencia Estatal de Investigación (España), Aspanoa, Asociación Carrera de la Mujer Ciudad de Monzón, ARAID Foundation, Asociación Española Contra el Cáncer, Ministerio de Ciencia, Innovación y Universidades (España), Ramírez-Labrada, Ariel [0000-0002-3888-7036], Pesini, Cecilia [0000-0002-8707-2722], Santiago, Llipsy [0000-0002-1861-5981], Hidalgo, Sandra [0000-0003-1629-9978], Uranga Murillo, Iratxe [0000-0001-8411-984X], Arias, Maykel [0000-0002-9730-2210], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Pardo, Julián [0000-0003-0154-0730], Ramírez-Labrada, Ariel, Pesini, Cecilia, Santiago, Llipsy, Hidalgo, Sandra, Calvo Pérez, Adanys, Oñate, Carmen, Andrés Tovar, Alejandro, Garzón Tituaña, Marcela, Uranga Murillo, Iratxe, Arias, Maykel, Gálvez Buerba, Eva Mª, Pardo, Julián, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), European Commission, Gobierno de Aragón, Agencia Estatal de Investigación (España), Aspanoa, Asociación Carrera de la Mujer Ciudad de Monzón, ARAID Foundation, Asociación Española Contra el Cáncer, Ministerio de Ciencia, Innovación y Universidades (España), Ramírez-Labrada, Ariel [0000-0002-3888-7036], Pesini, Cecilia [0000-0002-8707-2722], Santiago, Llipsy [0000-0002-1861-5981], Hidalgo, Sandra [0000-0003-1629-9978], Uranga Murillo, Iratxe [0000-0001-8411-984X], Arias, Maykel [0000-0002-9730-2210], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Pardo, Julián [0000-0003-0154-0730], Ramírez-Labrada, Ariel, Pesini, Cecilia, Santiago, Llipsy, Hidalgo, Sandra, Calvo Pérez, Adanys, Oñate, Carmen, Andrés Tovar, Alejandro, Garzón Tituaña, Marcela, Uranga Murillo, Iratxe, Arias, Maykel, Gálvez Buerba, Eva Mª, and Pardo, Julián
Abstract: NK cells are key mediators of immune cell-mediated cytotoxicity toward infected and transformed cells, being one of the main executors of cell death in the immune system. NK cells recognize target cells through an array of inhibitory and activating receptors for endogenous or exogenous pathogen-derived ligands, which together with adhesion molecules form a structure known as immunological synapse that regulates NK cell effector functions. The main and best characterized mechanisms involved in NK cell-mediated cytotoxicity are the granule exocytosis pathway (perforin/granzymes) and the expression of death ligands. These pathways are recognized as activators of different cell death programmes on the target cells leading to their destruction. However, most studies analyzing these pathways have used pure recombinant or native proteins instead of intact NK cells and, thus, extrapolation of the results to NK cell-mediated cell death might be difficult. Specially, since the activation of granule exocytosis and/or death ligands during NK cell-mediated elimination of target cells might be influenced by the stimulus received from target cells and other microenvironment components, which might affect the cell death pathways activated on target cells. Here we will review and discuss the available experimental evidence on how NK cells kill target cells, with a special focus on the different cell death modalities that have been found to be activated during NK cell-mediated cytotoxicity; including apoptosis and more inflammatory pathways like necroptosis and pyroptosis. In light of this new evidence, we will develop the new concept of cell death induced by NK cells as a new regulatory mechanism linking innate immune response with the activation of tumour adaptive T cell responses, which might be the initiating stimulus that trigger the cancer-immunity cycle. The use of the different cell death pathways and the modulation of the tumour cell molecular machinery regulating them might
Published: 2022

31. Adoptive NK cell transfer as a treatment in colorectal cancer patients: analyses of tumour cell determinants correlating with efficacy in vitro and in vivo

Author: Aspanoa, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), European Commission, Fundación Inocente Inocente, Asociación Carrera de la Mujer Ciudad de Monzón, Gobierno de Aragón, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), ARAID Foundation, Institut Català d'Oncologia, Ministerio de Economía, Industria y Competitividad (España), Centro de Investigación Biomédica en Red Epidemiología y Salud Pública (España), Agència de Gestió d'Ajuts Universitaris i de Recerca, European Cooperation in Science and Technology, Lanuza, Pilar M. [0000-0001-7328-2094], Alonso, M. Henar [0000-0003-0285-5451], Hidalgo, Sandra [0000-0003-1629-9978], Uranga Murillo, Iratxe [0000-0001-8411-984X], García-Mulero, Sandra [0000-0003-4931-1267], Sanjuan, Xavier [0000-0002-5253-822X], Santiago, Llipsy [0000-0002-1861-5981], Comas, Laura [0000-0002-3843-1231], Redrado, Sergio [0000-0002-8404-0012], Pazo-Cid, Roberto [0000-0002-8026-7391], Jaime Sánchez, Paula [0000-0002-8731-4269], Pesini, Cecilia [0000-0002-8707-2722], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Ramírez-Labrada, Ariel [0000-0002-3888-7036], Arias, Maykel [0000-0002-9730-2210], Sanz-Pamplona, Rebeca [0000-0002-2187-3527], Pardo, Julián [0000-0003-0154-0730], Lanuza, Pilar M., Alonso, M. Henar, Hidalgo, Sandra, Uranga Murillo, Iratxe, García-Mulero, Sandra, Arnau, Raquel, Santos Vivas, Cristina, Sanjuan, Xavier, Santiago, Llipsy, Comas, Laura, Redrado, Sergio, Pazo-Cid, Roberto, Agustín Ferrández, M. J., Jaime Sánchez, Paula, Pesini, Cecilia, Gálvez Buerba, Eva Mª, Ramírez-Labrada, Ariel, Arias, Maykel, Sanz-Pamplona, Rebeca, Pardo, Julián, Aspanoa, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), European Commission, Fundación Inocente Inocente, Asociación Carrera de la Mujer Ciudad de Monzón, Gobierno de Aragón, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), ARAID Foundation, Institut Català d'Oncologia, Ministerio de Economía, Industria y Competitividad (España), Centro de Investigación Biomédica en Red Epidemiología y Salud Pública (España), Agència de Gestió d'Ajuts Universitaris i de Recerca, European Cooperation in Science and Technology, Lanuza, Pilar M. [0000-0001-7328-2094], Alonso, M. Henar [0000-0003-0285-5451], Hidalgo, Sandra [0000-0003-1629-9978], Uranga Murillo, Iratxe [0000-0001-8411-984X], García-Mulero, Sandra [0000-0003-4931-1267], Sanjuan, Xavier [0000-0002-5253-822X], Santiago, Llipsy [0000-0002-1861-5981], Comas, Laura [0000-0002-3843-1231], Redrado, Sergio [0000-0002-8404-0012], Pazo-Cid, Roberto [0000-0002-8026-7391], Jaime Sánchez, Paula [0000-0002-8731-4269], Pesini, Cecilia [0000-0002-8707-2722], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Ramírez-Labrada, Ariel [0000-0002-3888-7036], Arias, Maykel [0000-0002-9730-2210], Sanz-Pamplona, Rebeca [0000-0002-2187-3527], Pardo, Julián [0000-0003-0154-0730], Lanuza, Pilar M., Alonso, M. Henar, Hidalgo, Sandra, Uranga Murillo, Iratxe, García-Mulero, Sandra, Arnau, Raquel, Santos Vivas, Cristina, Sanjuan, Xavier, Santiago, Llipsy, Comas, Laura, Redrado, Sergio, Pazo-Cid, Roberto, Agustín Ferrández, M. J., Jaime Sánchez, Paula, Pesini, Cecilia, Gálvez Buerba, Eva Mª, Ramírez-Labrada, Ariel, Arias, Maykel, Sanz-Pamplona, Rebeca, and Pardo, Julián
Abstract: [Background]: Colorectal cancer (CRC) is a heterogeneous disease with variable mutational profile and tumour microenvironment composition that influence tumour progression and response to treatment. While chemoresistant and poorly immunogenic CRC remains a challenge, the development of new strategies guided by biomarkers could help stratify and treat patients. Allogeneic NK cell transfer emerges as an alternative against chemoresistant and poorly immunogenic CRC., [Methods]: NK cell-related immunological markers were analysed by transcriptomics and immunohistochemistry in human CRC samples and correlated with tumour progression and overall survival. The anti-tumour ability of expanded allogeneic NK cells using a protocol combining cytokines and feeder cells was analysed in vitro and in vivo and correlated with CRC mutational status and the expression of ligands for immune checkpoint (IC) receptors regulating NK cell activity., [Results]: HLA-I downmodulation and NK cell infiltration correlated with better overall survival in patients with a low-stage (II) microsatellite instability-high (MSI-H) CRC, suggesting a role of HLA-I as a prognosis biomarker and a potential benefit of NK cell immunotherapy. Activated allogeneic NK cells were able to eliminate CRC cultures without PD-1 and TIM-3 restriction but were affected by HLA-I expression. In vivo experiments confirmed the efficacy of the therapy against both HLA+ and HLA− CRC cell lines. Concomitant administration of pembrolizumab failed to improve tumour control., [Conclusions]: Our results reveal an immunological profile of CRC tumours in which immunogenicity (MSI-H) and immune evasion mechanisms (HLA downmodulation) favour NK cell immunosurveillance at early disease stages. Accordingly, we have shown that allogeneic NK cell therapy can target tumours expressing mutations conferring poor prognosis regardless of the expression of T cell-related inhibitory IC ligands. Overall, this study provides a rationale for a new potential basis for CRC stratification and NK cell-based therapy.
Published: 2022

32. Integration of in silico and in vitro analysis of gliotoxin production reveals a narrow range of producing fungal species

Author: Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), European Commission, Gobierno de Aragón, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Aspanoa, Gilead Sciences, Asociación Carrera de la Mujer Ciudad de Monzón, ARAID Foundation, Redrado, Sergio [0000-0002-8404-0012], Esteban, Patricia [0000-0003-4123-3524], Domingo, María Pilar [0000-0002-6829-8769], Rezusta, Antonio [0000-0001-7294-245X], Ramírez-Labrada, Ariel [0000-0002-3888-7036], Arias, Maykel [0000-0002-9730-2210], Pardo, Julián [0000-0003-0154-0730], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Redrado, Sergio, Esteban, Patricia, Domingo, María Pilar, López Gómez, Concepción, Rezusta, Antonio, Ramírez-Labrada, Ariel, Arias, Maykel, Pardo, Julián, Gálvez Buerba, Eva Mª, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), European Commission, Gobierno de Aragón, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Aspanoa, Gilead Sciences, Asociación Carrera de la Mujer Ciudad de Monzón, ARAID Foundation, Redrado, Sergio [0000-0002-8404-0012], Esteban, Patricia [0000-0003-4123-3524], Domingo, María Pilar [0000-0002-6829-8769], Rezusta, Antonio [0000-0001-7294-245X], Ramírez-Labrada, Ariel [0000-0002-3888-7036], Arias, Maykel [0000-0002-9730-2210], Pardo, Julián [0000-0003-0154-0730], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Redrado, Sergio, Esteban, Patricia, Domingo, María Pilar, López Gómez, Concepción, Rezusta, Antonio, Ramírez-Labrada, Ariel, Arias, Maykel, Pardo, Julián, and Gálvez Buerba, Eva Mª
Abstract: Gliotoxin is a fungal secondary metabolite with impact on health and agriculture since it might act as virulence factor and contaminate human and animal food. Homologous gliotoxin (GT) gene clusters are spread across a number of fungal species although if they produce GT or other related epipolythiodioxopiperazines (ETPs) remains obscure. Using bioinformatic tools, we have identified homologous gli gene clusters similar to the A. fumigatus GT gene cluster in several fungal species. In silico study led to in vitro confirmation of GT and Bisdethiobis(methylthio)gliotoxin (bmGT) production in fungal strain cultures by HPLC detection. Despite we selected most similar homologous gli gene cluster in 20 different species, GT and bmGT were only detected in section Fumigati species and in a Trichoderma virens Q strain. Our results suggest that in silico gli homology analyses in different fungal strains to predict GT production might be only informative when accompanied by analysis about mycotoxin production in cell cultures.
Published: 2022

33. Antigen-specific primed cytotoxic T cells eliminate tumour cells in vivo and prevent tumour development, regardless of the presence of anti-apoptotic mutations conferring drug resistance

Author: Jaime-Sánchez, Paula, Catalán, Elena, Uranga-Murillo, Iratxe, Aguiló, Nacho, Santiago, Llipsy, M Lanuza, Pilar, de Miguel, Diego, A Arias, Maykel, and Pardo, Julián
Published: 2018
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34. Granzyme-A deficiency attenuates experimental osteoarthritis in mice, but perforin deficiency does not

Author: Calvo, Jorge, primary, Santiago, Llipsy, additional, Arias, Maykel, additional, Pardo, Julián, additional, Albareda, Jorge, additional, Martínez-Lostao, Luis, additional, and García-Alvarez, Felícito, additional
Published: 2023
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35. Granzyme-A deficiency attenuates experimental osteoarthritis in mice, but perforin deficiency does not

Author: Universidad de Zaragoza, European Commission, Gobierno de Aragón, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Ministerio de Ciencia e Innovación (España), Instituto de Salud Carlos III, Calvo Ibar, Jorge, Santiago, Llipsy, Arias, Maykel, Pardo, Julián, Albareda, Jorge, Martínez-Lostao, Luis, García-Alvarez, Felícito, Universidad de Zaragoza, European Commission, Gobierno de Aragón, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Ministerio de Ciencia e Innovación (España), Instituto de Salud Carlos III, Calvo Ibar, Jorge, Santiago, Llipsy, Arias, Maykel, Pardo, Julián, Albareda, Jorge, Martínez-Lostao, Luis, and García-Alvarez, Felícito
Abstract: [Objectives]: This study aims to assess the development of osteoarthritis (OA) in granzyme A- (gzmA) and B- (gzmB) and perforin- (perf) knockout mice., [Materials and methods]: A total of 75 male and female C57BL/6 (eight to nine-week-old) mice were allocated to: gzmA-deficient (gzmA-/-) (11 females, 8 males), gzmB-deficient (gzmB-/-) (9 females, 8 males), perf-deficient (perf-/-) (10 females, 9 males), and control group (10 females, 10 males). Osteoarthritis was induced in the right knee by instability of the meniscus medial ligament. Sham surgery was practiced in the left knee. Knee samples obtained eight weeks after surgery were stained (Safranin-O) and blindly scored in lateral and medial femur and tibia using the Osteoarthritis Research Society International scale (OARSI) (from Grade 0, cartilage intact to 6, deformation), (five stages from 0, no OA to 4, >50% surface involvement); OARSI score (grade x stage); and a semi-quantitative scale from Grade 0 (normal) to 6 (cartilage erosion >80%)., [Results]: Significantly higher values in all scales in the right knees compared to the left knees in male and female mice were observed (p<0.05). Males of all strains showed in the right knee higher values than females on all scales. Deficiency of perforin did not modify OA severity in any sex. The gzmA-/- females presented less degenerative changes than the other groups., [Conclusion]: Our study results show that sex plays an important role in the development of experimental OA in mice. Deficiency of gzmA can protect from the development of OA in female mice.
Published: 2023

36. Mouse Model of Colitis-Associated Colorectal Cancer (CAC): Isolation and Characterization of Mucosal-Associated Lymphoid Cells

Author: Santiago, Llipsy, primary, Castro, Marta, additional, Pardo, Julián, additional, and Arias, Maykel, additional
Published: 2018
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37. Fluorogenic Granzyme A Substrates Enable Real‐Time Imaging of Adaptive Immune Cell Activity

Author: Cheng, Zhiming, primary, Thompson, Emily J, additional, Mendive‐Tapia, Lorena, additional, Scott, Jamie I, additional, Benson, Sam, additional, Kitamura, Takanori, additional, Senan‐Salinas, Ana, additional, Samarakoon, Youhani, additional, Roberts, Edward W, additional, Arias, Maykel A, additional, Pardo, Julian, additional, Galvez, Eva M, additional, and Vendrell, Marc, additional
Published: 2023
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38. Fluorogenic Granzyme A Substrates Enable Real‐Time Imaging of Adaptive Immune Cell Activity

Author: Cheng, Zhiming, primary, Thompson, Emily J, additional, Mendive-Tapia, Lorena, additional, Scott, Jamie I, additional, Benson, Sam, additional, Kitamura, Takanori, additional, Senan-Salinas, Ana, additional, Samarakoon, Youhani, additional, Roberts, Edward W, additional, Arias, Maykel A., additional, Pardo, Julian, additional, Galvez, Eva M, additional, and Vendrell, Marc, additional
Published: 2022
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39. Cleavage of cFLIP restrains cell death during viral infection and tissue injury and favors tissue repair

Author: Martinez Lagunas, Kristel, primary, Savcigil, Deniz Pinar, additional, Zrilic, Matea, additional, Carvajal Fraile, Carlos, additional, Craxton, Andrew, additional, Self, Emily, additional, Uranga-Murillo, Iratxe, additional, de Miguel, Diego, additional, Arias, Maykel, additional, Willenborg, Sebastian, additional, Piekarek, Michael, additional, Albert, Marie Christine, additional, Nugraha, Kalvin, additional, Lisewski, Ina, additional, Janakova, Erika, additional, Igual, Natalia, additional, Tonnus, Wulf, additional, Hildebrandt, Ximena, additional, Ibrahim, Mohammed, additional, Ballegeer, Marlies, additional, Saelens, Xavier, additional, Kueh, Andrew, additional, Meier, Pascal, additional, Linkermann, Andreas, additional, Pardo, Julian, additional, Eming, Sabine, additional, Walczak, Henning, additional, MacFarlane, Marion, additional, Peltzer, Nieves, additional, and Annibaldi, Alessandro, additional
Published: 2022
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40. A cross-sectional serosurvey of SARS-CoV-2 and co-infections in stray cats from the second wave to the sixth wave of COVID-19 outbreaks in Spain

Author: Villanueva-Saz, Sergio, primary, Martínez, Mariví, additional, Giner, Jacobo, additional, González, Ana, additional, Tobajas, Ana Pilar, additional, Pérez, María Dolores, additional, Lira-Navarrete, Erandi, additional, González-Ramírez, Andrés Manuel, additional, Macías-León, Javier, additional, Verde, Maite, additional, Yzuel, Andrés, additional, Hurtado-Guerrero, Ramón, additional, Arias, Maykel, additional, Santiago, Llipsy, additional, Aguiló-Gisbert, Jordi, additional, Ruíz, Héctor, additional, Lacasta, Delia, additional, Marteles, Diana, additional, and Fernández, Antonio, additional
Published: 2022
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41. Granzyme A inhibition reduces inflammation and increases survival during abdominal sepsis

Author: Garzón, Marcela [0000-0001-6778-0636], Comas, Laura [0000-0002-3843-1231], Santiago, Llipsy [0000-0002-1861-5981], Uranga Murillo, Iratxe [0000-0001-8411-984X], Ramírez-Labrada, Ariel [0000-0002-3888-7036], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Pardo, Julián [0000-0003-0154-0730], Arias, Maykel [0000-0002-9730-2210], Garzón, Marcela, Comas, Laura, Santiago, Llipsy, Uranga Murillo, Iratxe, Ramírez-Labrada, Ariel, Gálvez Buerba, Eva Mª, Pardo, Julián, Arias, Maykel, Garzón, Marcela [0000-0001-6778-0636], Comas, Laura [0000-0002-3843-1231], Santiago, Llipsy [0000-0002-1861-5981], Uranga Murillo, Iratxe [0000-0001-8411-984X], Ramírez-Labrada, Ariel [0000-0002-3888-7036], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Pardo, Julián [0000-0003-0154-0730], Arias, Maykel [0000-0002-9730-2210], Garzón, Marcela, Comas, Laura, Santiago, Llipsy, Uranga Murillo, Iratxe, Ramírez-Labrada, Ariel, Gálvez Buerba, Eva Mª, Pardo, Julián, and Arias, Maykel
Abstract: Peritonitis is one of the most common causes of sepsis. Evidence suggests that Granzyme A (GzmA), a serine protease mainly expressed by NK and T cells, could act as proinflammatory mediator and could play an important role in the pathogenesis of sepsis. Here, we aim to analyze the role and therapeutic potential of GzmA in the pathogenesis of peritoneal sepsis.
Published: 2021

42. Determination of the concentration of IgG against the spike receptor-binding domain that predicts the viral neutralizing activity of convalescent plasma and serum against SARS-CoV-2

Author: Gobierno de Aragón, Fundación Banco Santander, Universidad de Zaragoza, Instituto de Salud Carlos III, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Fundación Inocente Inocente, Aspanoa, Asociación Carrera de la Mujer Ciudad de Monzón, ARAID Foundation, Santiago, Llipsy [0000-0002-1861-5981], Uranga Murillo, Iratxe [0000-0001-8411-984X], Arias, Maykel [0000-0002-9730-2210], González Ramírez, Andrés Manuel [0000-0002-5838-0857], Macías León, Javier [0000-0001-6815-6720], Moreo, Eduardo [0000-0002-0182-201X], Redrado, Sergio [0000-0002-8404-0012], Taleb, V. [0000-0001-9224-5854], Lira-Navarrete, Erandi [0000-0003-2462-7580], Hurtado-Guerrero, R. [0000-0002-3122-9401], Encabo-Berzosa, M. Mar [0000-0001-5533-804X], Hidalgo, Sandra [0000-0003-1629-9978], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Ramírez-Labrada, Ariel [0000-0002-3888-7036], Miguel, Diego de [0000-0002-8486-8514], Benito, Rafael [0000-0001-5134-1006], Fernández Casanovas, Antonio [0000-0002-2557-4890], Serrano Barcos, Laura [0000-0002-9291-9801], Yuste, Cristina [0000-0003-3667-523X], Villanueva-Saz, Sergio [0000-0001-6209-4282], Paño, José Ramón [0000-0002-9600-8116], Pardo, Julián [0000-0003-0154-0730], Santiago, Llipsy, Uranga Murillo, Iratxe, Arias, Maykel, González Ramírez, Andrés Manuel, Macías-León, Javier, Moreo, Eduardo, Redrado, Sergio, García García, Ana, Taleb, V., Lira-Navarrete, Erandi, Hurtado-Guerrero, R., Aguiló, Nacho, Encabo-Berzosa, M. Mar, Hidalgo, Sandra, Gálvez Buerba, Eva Mª, Ramírez-Labrada, Ariel, Miguel, Diego de, Benito, Rafael, Miranda, Patricia, Fernández Casanovas, Antonio, Domingo, José María, Serrano Barcos, Laura, Yuste, Cristina, Villanueva-Saz, Sergio, Paño, José Ramón, Pardo, Julián, Gobierno de Aragón, Fundación Banco Santander, Universidad de Zaragoza, Instituto de Salud Carlos III, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Fundación Inocente Inocente, Aspanoa, Asociación Carrera de la Mujer Ciudad de Monzón, ARAID Foundation, Santiago, Llipsy [0000-0002-1861-5981], Uranga Murillo, Iratxe [0000-0001-8411-984X], Arias, Maykel [0000-0002-9730-2210], González Ramírez, Andrés Manuel [0000-0002-5838-0857], Macías León, Javier [0000-0001-6815-6720], Moreo, Eduardo [0000-0002-0182-201X], Redrado, Sergio [0000-0002-8404-0012], Taleb, V. [0000-0001-9224-5854], Lira-Navarrete, Erandi [0000-0003-2462-7580], Hurtado-Guerrero, R. [0000-0002-3122-9401], Encabo-Berzosa, M. Mar [0000-0001-5533-804X], Hidalgo, Sandra [0000-0003-1629-9978], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Ramírez-Labrada, Ariel [0000-0002-3888-7036], Miguel, Diego de [0000-0002-8486-8514], Benito, Rafael [0000-0001-5134-1006], Fernández Casanovas, Antonio [0000-0002-2557-4890], Serrano Barcos, Laura [0000-0002-9291-9801], Yuste, Cristina [0000-0003-3667-523X], Villanueva-Saz, Sergio [0000-0001-6209-4282], Paño, José Ramón [0000-0002-9600-8116], Pardo, Julián [0000-0003-0154-0730], Santiago, Llipsy, Uranga Murillo, Iratxe, Arias, Maykel, González Ramírez, Andrés Manuel, Macías-León, Javier, Moreo, Eduardo, Redrado, Sergio, García García, Ana, Taleb, V., Lira-Navarrete, Erandi, Hurtado-Guerrero, R., Aguiló, Nacho, Encabo-Berzosa, M. Mar, Hidalgo, Sandra, Gálvez Buerba, Eva Mª, Ramírez-Labrada, Ariel, Miguel, Diego de, Benito, Rafael, Miranda, Patricia, Fernández Casanovas, Antonio, Domingo, José María, Serrano Barcos, Laura, Yuste, Cristina, Villanueva-Saz, Sergio, Paño, José Ramón, and Pardo, Julián
Abstract: Passive immunization with hyperimmune plasma from convalescent patients has been proposed as a potentially useful treatment for COVID-19. Nevertheless, its efficacy in patients with COVID-19 remains uncertain. Thus, the establishment and validation of standardized methods that predict the viral neutralizing (VN) activity of plasma against SARS-CoV-2 is of utmost importance to appraise its therapeutic value. Using an in-house quantitative ELISA test and two independent cohorts with a total of 345 donors, we found that plasma and serum from most convalescent donors contained IgG antibodies specific to the spike receptor-binding domain (RBD) of SARS-CoV-2, with varying concentrations which correlate with previous disease severity and gender. Anti-RBD IgG plasma concentration significantly correlated with the plasma/serum VN activity against SARS-CoV-2 in vitro., Several hundred millions of people have been diagnosed of coronavirus disease 2019 (COVID-19), causing millions of deaths and a high socioeconomic burden. SARS-CoV-2, the causative agent of COVID-19, induces both specific T- and B-cell responses, being antibodies against the virus detected a few days after infection. Passive immunization with hyperimmune plasma from convalescent patients has been proposed as a potentially useful treatment for COVID-19. Using an in-house quantitative ELISA test, we found that plasma from 177 convalescent donors contained IgG antibodies specific to the spike receptor-binding domain (RBD) of SARS-CoV-2, although at very different concentrations which correlated with previous disease severity and gender. Anti-RBD IgG plasma concentrations significantly correlated with the plasma viral neutralizing activity (VN) against SARS-CoV-2 in vitro. Similar results were found using an independent cohort of serum from 168 convalescent health workers. These results validate an in-house RBD IgG ELISA test in a large cohort of COVID-19 convalescent patients and indicate that plasma from all convalescent donors does not contain a high enough amount of anti-SARS-CoV-2-RBD neutralizing IgG to prevent SARS-CoV-2 infection in vitro. The use of quantitative anti-RBD IgG detection systems might help to predict the efficacy of the passive immunization using plasma from patients recovered from SARS-CoV-2.
Published: 2021

43. In vitro and in vivo antibacterial activity of gliotoxin alone and in combination with antibiotics against staphylococcus aureus

Author: European Commission, Gobierno de Aragón, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Aspanoa, Gilead Sciences, Asociación Carrera de la Mujer Ciudad de Monzón, ARAID Foundation, Esteban, Patricia [0000-0003-4123-3524], Redrado, Sergio [0000-0002-8404-0012], Comas, Laura [0000-0002-3843-1231], Domingo, María Pilar [0000-0002-6829-8769], Algarate, Sonia [0000-0002-0036-663], Rezusta, Antonio [0000-0001-7294-245X], Pardo, Julián [0000-0003-0154-0730], Arias, Maykel [0000-0002-9730-2210], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Esteban, Patricia, Redrado, Sergio, Comas, Laura, Domingo, María Pilar, Millán-Lou, María Isabel, Seral, Cristina, Algarate, Sonia, López Gómez, Concepción, Rezusta, Antonio, Pardo, Julián, Arias, Maykel, Gálvez Buerba, Eva Mª, European Commission, Gobierno de Aragón, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Aspanoa, Gilead Sciences, Asociación Carrera de la Mujer Ciudad de Monzón, ARAID Foundation, Esteban, Patricia [0000-0003-4123-3524], Redrado, Sergio [0000-0002-8404-0012], Comas, Laura [0000-0002-3843-1231], Domingo, María Pilar [0000-0002-6829-8769], Algarate, Sonia [0000-0002-0036-663], Rezusta, Antonio [0000-0001-7294-245X], Pardo, Julián [0000-0003-0154-0730], Arias, Maykel [0000-0002-9730-2210], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Esteban, Patricia, Redrado, Sergio, Comas, Laura, Domingo, María Pilar, Millán-Lou, María Isabel, Seral, Cristina, Algarate, Sonia, López Gómez, Concepción, Rezusta, Antonio, Pardo, Julián, Arias, Maykel, and Gálvez Buerba, Eva Mª
Abstract: Multidrug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) is one of the major causes of hospital-acquired and community infections and pose a challenge to the human health care system. Therefore, it is important to find new drugs that show activity against these bacteria, both in monotherapy and in combination with other antimicrobial drugs. Gliotoxin (GT) is a mycotoxin produced by Aspergillus fumigatus and other fungi of the Aspergillus genus. Some evidence suggests that GT shows antimicrobial activity against S. aureus in vitro, albeit its efficacy against multidrug-resistant strains such as MRSA or vancomycin-intermediate S. aureus (VISA) strainsis not known. This work aimed to evaluate the antibiotic efficacy of GT as monotherapy or in combination with other therapeutics against MRSA in vitro and in vivo using a Caenorhabditis elegans infection model.
Published: 2021

44. Análisis de la actividad antimicrobiana de la Gliotoxina en diferentes microorganismos de interés clínico

Author: Esteban, Patricia [0000-0003-4123-3524], Arias, Maykel [0000-0002-9730-2210], Redrado, Sergio [0000-0002-8404-0012], Domingo, María Pilar [0000-0002-6829-8769], Pardo, Julián [0000-0003-0154-0730], Rezusta, Antonio [0000-0001-7294-245X], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Esteban, Patricia, Arias, Maykel, Millán-Lou, María Isabel, Redrado, Sergio, Domingo, María Pilar, García, Matilde, Gómez Lapuente, María Ángeles, Roc, Lourdes, López Gómez, Concepción, Pardo, Julián, Rezusta, Antonio, Gálvez Buerba, Eva Mª, Esteban, Patricia [0000-0003-4123-3524], Arias, Maykel [0000-0002-9730-2210], Redrado, Sergio [0000-0002-8404-0012], Domingo, María Pilar [0000-0002-6829-8769], Pardo, Julián [0000-0003-0154-0730], Rezusta, Antonio [0000-0001-7294-245X], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Esteban, Patricia, Arias, Maykel, Millán-Lou, María Isabel, Redrado, Sergio, Domingo, María Pilar, García, Matilde, Gómez Lapuente, María Ángeles, Roc, Lourdes, López Gómez, Concepción, Pardo, Julián, Rezusta, Antonio, and Gálvez Buerba, Eva Mª
Abstract: [Introducción/Objetivos]: la gliotoxina es una micotoxina producida por Aspergillus fumigatus y otros hongos del género Aspergillus. Es un metabolito secundario perteneciente a la familia de las epipolitiodioxopiperazinas, caracterizada por la presencia de un puente disulfuro interno en un anillo de piperazina, que parece ser necesario para la mayoría de las propiedades biológicas de este compuesto. Se ha demostrado que la gliotoxina es un factor de virulencia durante la aspergilosis invasiva y presenta una toxicidad notable contra las células de mamíferos. Sin embargo, las evidencias científicas sobre su potencial actividad antimicrobiana son escasas. Por lo tanto, este trabajo tiene como objetivo evaluar su eficacia antibiótica contra microorganismos de interés clínico como Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa; y antifúngico contra Candida albicans y Candida glabrata. [Material y métodos]: la sensibilidad a la gliotoxina de diferentes cepas (incluidas las farmacorresistentes) de los microorganismos indicados se analizó por diferentes métodos: métodos de difusión en disco (antibiogramas/antifungigramas), estudio de curvas de tiempo-mortalidad, métodos de microdilución y ensayo MTT. Para los aislados de Candida, los resultados fueron confirmados mediante el análisis de la muerte celular por citometría de flujo. [Resultados]: Los resultados sugieren una potente actividad antimicrobiana de gliotoxina contra Candida albicans y Staphylococcus aureus, incluso en las cepas resistentes a azoles y a meticilina, respectivamente. En el caso de Escherichia coli y Candida glabrata, la gliotoxina ejerce una acción antimicrobiana moderada. Sin embargo, Pseudomonas aeruginosa parece ser resistente a la gliotoxina. [Conclusiones]: Nuestros resultados indican que la gliotoxina es efectiva contra Candida albicans y Staphylococcus aureus por lo que podría usarse como una alternativa para el tratamiento de infecciones causadas por cepas resistentes a antibiót
Published: 2021

45. Inﬂammatory cell death induced by cytotoxic lymphocytes: a dangerous but necessary liaison

Author: European Commission, Gobierno de Aragón, Ministerio de Ciencia, Innovación y Universidades (España), Instituto de Salud Carlos III, Agencia Estatal de Investigación (España), Fundación Inocente Inocente, Aspanoa, Asociación Carrera de la Mujer Ciudad de Monzón, ARAID Foundation, de Miguel, Diego [0000-0002-8486-8514], Ramírez-Labrada, Ariel [0000-0002-3888-7036], Uranga Murillo, Iratxe [0000-0001-8411-984X], Hidalgo, Sandra [0000-0003-1629-9978], Santiago, Llipsy [0000-0002-1861-5981], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Arias, Maykel [0000-0002-9730-2210], Pardo, Julián [0000-0003-0154-0730], Miguel, Diego de, Ramírez-Labrada, Ariel, Uranga Murillo, Iratxe, Hidalgo, Sandra, Santiago, Llipsy, Gálvez Buerba, Eva Mª, Arias, Maykel, Pardo, Julián, European Commission, Gobierno de Aragón, Ministerio de Ciencia, Innovación y Universidades (España), Instituto de Salud Carlos III, Agencia Estatal de Investigación (España), Fundación Inocente Inocente, Aspanoa, Asociación Carrera de la Mujer Ciudad de Monzón, ARAID Foundation, de Miguel, Diego [0000-0002-8486-8514], Ramírez-Labrada, Ariel [0000-0002-3888-7036], Uranga Murillo, Iratxe [0000-0001-8411-984X], Hidalgo, Sandra [0000-0003-1629-9978], Santiago, Llipsy [0000-0002-1861-5981], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Arias, Maykel [0000-0002-9730-2210], Pardo, Julián [0000-0003-0154-0730], Miguel, Diego de, Ramírez-Labrada, Ariel, Uranga Murillo, Iratxe, Hidalgo, Sandra, Santiago, Llipsy, Gálvez Buerba, Eva Mª, Arias, Maykel, and Pardo, Julián
Abstract: Cytotoxic lymphocytes (CLs), and more specifically Tc and NK cells, are the main executors of cell death in the immune system, playing a key role during both immunosurveillance and immunotherapy. These cells induce regulated cell death (RCD) by different mechanisms, being granular exocytosis and expression of death ligands the most prominent and best characterized ones. Apoptosis, a traditionally considered low-inflammatory type of cell death, has been accepted for years as the paradigm of RCD induced by CLs. However, several recent studies have demonstrated that NK cells and Tc cells can also induce more inflammatory forms of cell death, namely, necroptosis, pyroptosis, and ferroptosis. Activation of these highly inflammatory types of cell death appears to critically contribute to the activation of a successful antitumour immune response. Additionally, the role of specific cell death pathways in immunogenic cell death is still under intense debate, especially considering the interconnections with other inflammatory forms of cell death. These evidences, together with the advent of new cancer immunotherapies, highlight the necessity to deepen our understanding of the link between the cell death triggered by CLs and inflammation. This knowledge will be instrumental to maximize the antitumour potential of immunotherapies, minimizing deleterious effects associated with these treatments. In this review, we will briefly summarize the main features of apoptosis, necroptosis, pyroptosis and ferroptosis, to subsequently discuss the most recent evidences about the role of these RCD pathways during the elimination of cancer cells mediated by CLs and its modulation to increase the efficacy of cancer immunotherapy.
Published: 2021

46. The New Strains Brucella inopinata BO1 and Brucella Species 83-210 Behave Biologically Like Classic Infectious Brucella Species and Cause Death in Murine Models of Infection

Author: de Bagüés, María P. Jiménez, Iturralde, María, Arias, Maykel A., Pardo, Julián, Cloeckaert, Axel, and Zygmunt, Michel S.
Published: 2014

47. Análisis de la actividad antimicrobiana de la Gliotoxina en diferentes microorganismos de interés clínico

Author: Esteban, Patricia, Arias, Maykel, Millán-Lou, María Isabel, Redrado, Sergio, Domingo, María Pilar, García, Matilde, Gómez Lapuente, María Ángeles, Roc, Lourdes, López Gómez, Concepción, Pardo, Julián, Rezusta, Antonio, Gálvez Buerba, Eva Mª, Esteban, Patricia, Arias, Maykel, Redrado, Sergio, Domingo, María Pilar, Pardo, Julián, Rezusta, Antonio, Gálvez Buerba, Eva Mª, Esteban, Patricia [0000-0003-4123-3524], Arias, Maykel [0000-0002-9730-2210], Redrado, Sergio [0000-0002-8404-0012], Domingo, María Pilar [0000-0002-6829-8769], Pardo, Julián [0000-0003-0154-0730], Rezusta, Antonio [0000-0001-7294-245X], and Gálvez Buerba, Eva Mª [0000-0001-6928-5516]
Subjects: Micotoxina, Modelo animal, Gliotoxina, Antimicrobiano
Abstract: Trabajo presentado en el XXIV Congreso Nacional de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC), celebrado de manera virtual del 5-11 junio de 2021., [Introducción/Objetivos]: la gliotoxina es una micotoxina producida por Aspergillus fumigatus y otros hongos del género Aspergillus. Es un metabolito secundario perteneciente a la familia de las epipolitiodioxopiperazinas, caracterizada por la presencia de un puente disulfuro interno en un anillo de piperazina, que parece ser necesario para la mayoría de las propiedades biológicas de este compuesto. Se ha demostrado que la gliotoxina es un factor de virulencia durante la aspergilosis invasiva y presenta una toxicidad notable contra las células de mamíferos. Sin embargo, las evidencias científicas sobre su potencial actividad antimicrobiana son escasas. Por lo tanto, este trabajo tiene como objetivo evaluar su eficacia antibiótica contra microorganismos de interés clínico como Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa; y antifúngico contra Candida albicans y Candida glabrata. [Material y métodos]: la sensibilidad a la gliotoxina de diferentes cepas (incluidas las farmacorresistentes) de los microorganismos indicados se analizó por diferentes métodos: métodos de difusión en disco (antibiogramas/antifungigramas), estudio de curvas de tiempo-mortalidad, métodos de microdilución y ensayo MTT. Para los aislados de Candida, los resultados fueron confirmados mediante el análisis de la muerte celular por citometría de flujo. [Resultados]: Los resultados sugieren una potente actividad antimicrobiana de gliotoxina contra Candida albicans y Staphylococcus aureus, incluso en las cepas resistentes a azoles y a meticilina, respectivamente. En el caso de Escherichia coli y Candida glabrata, la gliotoxina ejerce una acción antimicrobiana moderada. Sin embargo, Pseudomonas aeruginosa parece ser resistente a la gliotoxina. [Conclusiones]: Nuestros resultados indican que la gliotoxina es efectiva contra Candida albicans y Staphylococcus aureus por lo que podría usarse como una alternativa para el tratamiento de infecciones causadas por cepas resistentes a antibióticos/antifúngicos. Sin embargo, será necesario aclarar aún más los mecanismos por los cuales la gliotoxina ejerce este efecto y probar en modelos apropiados in vivo la viabilidad de su uso teniendo en cuenta los posibles efectos secundarios debido a su toxicidad. En este sentido, planeamos analizar su eficacia y seguridad en un modelo de infección cutánea causada por Staphylococcus aureus.
Published: 2021

48. Granzyme A inhibition reduces inflammation and increases survival during abdominal sepsis

Author: Garzón, Marcela, Comas, Laura, Santiago, Llipsy, Uranga Murillo, Iratxe, Ramírez-Labrada, Ariel, Gálvez Buerba, Eva Mª, Pardo, Julián, Arias, Maykel, Garzón, Marcela [0000-0001-6778-0636], Comas, Laura [0000-0002-3843-1231], Santiago, Llipsy [0000-0002-1861-5981], Uranga Murillo, Iratxe [0000-0001-8411-984X], Ramírez-Labrada, Ariel [0000-0002-3888-7036], Gálvez Buerba, Eva Mª [0000-0001-6928-5516], Pardo, Julián [0000-0003-0154-0730], Arias, Maykel [0000-0002-9730-2210], Garzón, Marcela, Comas, Laura, Santiago, Llipsy, Uranga Murillo, Iratxe, Ramírez-Labrada, Ariel, Gálvez Buerba, Eva Mª, Pardo, Julián, and Arias, Maykel
Subjects: Inflammation, Sepsis, Granzyme A, Cecal ligation and puncture, Peritonitis
Abstract: 3 figuras.-- Póster presentado en el 42º Congreso SEI, Congreso de la Sociedad Española de Inmunología, formato virtual, 24-26 marzo de 2021, Madrid., Peritonitis is one of the most common causes of sepsis. Evidence suggests that Granzyme A (GzmA), a serine protease mainly expressed by NK and T cells, could act as proinflammatory mediator and could play an important role in the pathogenesis of sepsis. Here, we aim to analyze the role and therapeutic potential of GzmA in the pathogenesis of peritoneal sepsis.
Published: 2021

49. Ultrastructural analysis and three-dimensional reconstruction of cellular structures involved in SARS-CoV-2 spread

Author: Baselga, Marta, primary, Moreo, Eduardo, additional, Uranga-Murillo, Iratxe, additional, Arias, Maykel, additional, and Junquera, Concepción, additional
Published: 2022
Full Text: View/download PDF

50. Silver Nanoparticles–Polyethyleneimine-Based Coatings with Antiviral Activity against SARS-CoV-2: A New Method to Functionalize Filtration Media

Author: Baselga, Marta, primary, Uranga-Murillo, Iratxe, additional, de Miguel, Diego, additional, Arias, Maykel, additional, Sebastián, Victor, additional, Pardo, Julián, additional, and Arruebo, Manuel, additional
Published: 2022
Full Text: View/download PDF

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