109 results on '"La Manna, Marco Pio"'
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2. Correction: Shekarkar Azgomi et al. A Rapid and Simple Multiparameter Assay to Quantify Spike-Specific CD4 and CD8 T Cells after SARS-CoV-2 Vaccination: A Preliminary Report. Biomedicines 2021, 9, 1576
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Shekarkar Azgomi, Mojtaba, primary, La Manna, Marco Pio, additional, Badami, Giusto Davide, additional, Ragonese, Paolo, additional, Trizzino, Antonino, additional, Dieli, Francesco, additional, and Caccamo, Nadia, additional
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- 2023
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3. Emerging Roles of Cells and Molecules of Innate Immunity in Alzheimer’s Disease
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Tamburini, Bartolo, primary, Badami, Giusto Davide, additional, La Manna, Marco Pio, additional, Shekarkar Azgomi, Mojtaba, additional, Caccamo, Nadia, additional, and Dieli, Francesco, additional
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- 2023
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4. B-Cell Receptor Signaling Is Thought to Be a Bridge between Primary Sjogren Syndrome and Diffuse Large B-Cell Lymphoma
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Mohammadnezhad, Leila, primary, Shekarkar Azgomi, Mojtaba, additional, La Manna, Marco Pio, additional, Guggino, Giuliana, additional, Botta, Cirino, additional, Dieli, Francesco, additional, and Caccamo, Nadia, additional
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- 2023
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5. The Abundance of Tumor-Infiltrating CD8+ Tissue Resident Memory T Lymphocytes Correlates with Patient Survival in Glioblastoma
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La Manna, Marco Pio, primary, Di Liberto, Diana, additional, Lo Pizzo, Marianna, additional, Mohammadnezhad, Leila, additional, Shekarkar Azgomi, Mojtaba, additional, Salamone, Vincenzo, additional, Cancila, Valeria, additional, Vacca, Davide, additional, Dieli, Costanza, additional, Maugeri, Rosario, additional, Brunasso, Lara, additional, Iacopino, Domenico Gerardo, additional, Dieli, Francesco, additional, and Caccamo, Nadia, additional
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- 2022
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6. Downregulation of miRNA17–92 cluster marks Vγ9Vδ2 T cells from patients with rheumatoid arthritis
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Guggino, Giuliana, Orlando, Valentina, Saieva, Laura, Ruscitti, Piero, Cipriani, Paola, La Manna, Marco Pio, Giacomelli, Roberto, Alessandro, Riccardo, Triolo, Giovanni, Ciccia, Francesco, Dieli, Francesco, and Caccamo, Nadia
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- 2018
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7. Interleukin-6 Is a Promising Marker of COVID-19 in Children: A Case Series of 2 Brothers with Severe COVID-19 Pneumonia
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Maggio, Maria Cristina, primary, Failla, Maria Concetta, additional, Giordano, Salvatore, additional, La Manna, Marco Pio, additional, and Sireci, Guido, additional
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- 2022
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8. Phenotypic and Immunometabolic Aspects on Stem Cell Memory and Resident Memory CD8+ T Cells
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La Manna, Marco Pio, primary, Shekarkar Azgomi, Mojtaba, additional, Tamburini, Bartolo, additional, Badami, Giusto Davide, additional, Mohammadnezhad, Leila, additional, Dieli, Francesco, additional, and Caccamo, Nadia, additional
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- 2022
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9. Metabolic Reprogramming of Innate Immune Cells as a Possible Source of New Therapeutic Approaches in Autoimmunity
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Mohammadnezhad, Leila, primary, Shekarkar Azgomi, Mojtaba, additional, La Manna, Marco Pio, additional, Sireci, Guido, additional, Rizzo, Chiara, additional, Badami, Giusto Davide, additional, Tamburini, Bartolo, additional, Dieli, Francesco, additional, Guggino, Giuliana, additional, and Caccamo, Nadia, additional
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- 2022
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10. Reversible Effect of Magnetic Fields on Human Lymphocyte Activation Patterns: Different Sensitivity of Naive and Memory Lymphocyte Subsets
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Salerno, Sergio, La Mendola, Carmela, La Manna, Marco Pio, Casto, Antonio Lo, Caccamo, Nadia, and Salerno, Alfredo
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- 2009
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11. Immunity and Nutrition: The Right Balance in Inflammatory Bowel Disease
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Tamburini, Bartolo, primary, La Manna, Marco Pio, additional, La Barbera, Lidia, additional, Mohammadnezhad, Leila, additional, Badami, Giusto Davide, additional, Shekarkar Azgomi, Mojtaba, additional, Dieli, Francesco, additional, and Caccamo, Nadia, additional
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- 2022
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12. Tumor-Derived Small Extracellular Vesicles Induce Pro-Inflammatory Cytokine Expression and PD-L1 Regulation in M0 Macrophages via IL-6/STAT3 and TLR4 Signaling Pathways
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Pucci, Marzia, primary, Raimondo, Stefania, additional, Urzì, Ornella, additional, Moschetti, Marta, additional, Di Bella, Maria Antonietta, additional, Conigliaro, Alice, additional, Caccamo, Nadia, additional, La Manna, Marco Pio, additional, Fontana, Simona, additional, and Alessandro, Riccardo, additional
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- 2021
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13. Potential involvement of IL-9 and Th9 cells in the pathogenesis of rheumatoid arthritis
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Ciccia, Francesco, Guggino, Giuliana, Rizzo, Aroldo, Manzo, Antonio, Vitolo, Barbara, La Manna, Marco Pio, Giardina, Giuseppina, Sireci, Guido, Dieli, Francesco, Montecucco, Carlo Maurizio, Alessandro, Riccardo, and Triolo, Giovanni
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- 2015
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14. The Abundance of Tumor-Infiltrating CD8 + Tissue Resident Memory T Lymphocytes Correlates with Patient Survival in Glioblastoma.
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La Manna, Marco Pio, Di Liberto, Diana, Lo Pizzo, Marianna, Mohammadnezhad, Leila, Shekarkar Azgomi, Mojtaba, Salamone, Vincenzo, Cancila, Valeria, Vacca, Davide, Dieli, Costanza, Maugeri, Rosario, Brunasso, Lara, Iacopino, Domenico Gerardo, Dieli, Francesco, and Caccamo, Nadia
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T cells ,OVERALL survival ,GLIOBLASTOMA multiforme ,CD8 antigen ,LYMPHOCYTE subsets - Abstract
Glial tumors alone account for 40% of all CNS tumors and present a low survival rate. The tumor microenvironment is a critical regulator of tumor progression and therapeutic effectiveness in glioma. Growing evidence from numerous studies of human solid tumor-infiltrating CD8
+ T cells indicates that tissue-resident memory T cells (TRM) represent a substantial subpopulation of tumor-infiltrating lymphocytes (TILs). Although it is reported that some types of cancer patients with high immune infiltration tend to have better outcomes than patients with low immune infiltration, it seems this does not happen in gliomas. This study aimed to characterize TRMs cells in the glioma tumor microenvironment to identify their potential predictive and prognostic role and the possible therapeutic applications. Fluorescence activated cell sorting (FACS) analysis and immunofluorescence staining highlighted a statistically significant increase in CD8+ TRM cells (CD103+ and CD69+ CD8+ T cells) in gliomas compared to control samples (meningioma). In-silico analysis of a dataset of n = 153 stage IV glioma patients confirmed our data. Moreover, the gene expression analysis showed an increase in the expression of TRM-related genes in tumor tissues compared to normal tissues. This analysis also highlighted the positive correlation between genes associated with CD8+ TRM and TILs, indicating that CD8+ TRMs cells are present among the infiltrating T cells. Finally, high expression of Integrin subunit alpha E (ITGAE), the gene coding for the integrin CD103, and high CD8+ TILs abundance were associated with more prolonged survival, whereas high ITGAE expression but low CD8+ TILs abundance were associated with lower survival. [ABSTRACT FROM AUTHOR]- Published
- 2022
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15. Phenotypic and Immunometabolic Aspects on Stem Cell Memory and Resident Memory CD8+ T Cells.
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La Manna, Marco Pio, Shekarkar Azgomi, Mojtaba, Tamburini, Bartolo, Badami, Giusto Davide, Mohammadnezhad, Leila, Dieli, Francesco, and Caccamo, Nadia
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IMMUNOLOGIC memory ,STEM cells ,IMMUNE response ,MEMORY ,PHENOTYPES - Abstract
The immune system, smartly and surprisingly, saves the exposure of a particular pathogen in its memory and reacts to the pathogen very rapidly, preventing serious diseases. Immunologists have long been fascinated by understanding the ability to recall and respond faster and more vigorously to a pathogen, known as "memory". T-cell populations can be better described by using more sophisticated techniques to define phenotype, transcriptional and epigenetic signatures and metabolic pathways (single-cell resolution), which uncovered the heterogeneity of the memory T-compartment. Phenotype, effector functions, maintenance, and metabolic pathways help identify these different subsets. Here, we examine recent developments in the characterization of the heterogeneity of the memory T cell compartment. In particular, we focus on the emerging role of CD8
+ TRM and TSCM cells, providing evidence on how their immunometabolism or modulation can play a vital role in their generation and maintenance in chronic conditions such as infections or autoimmune diseases. [ABSTRACT FROM AUTHOR]- Published
- 2022
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16. Immune Response to Tick-Borne Hemoparasites: Host Adaptive Immune Response Mechanisms as Potential Targets for Therapies and Vaccines
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Torina, Alessandra, primary, Blanda, Valeria, additional, Villari, Sara, additional, Piazza, Antonio, additional, La Russa, Francesco, additional, Grippi, Francesca, additional, La Manna, Marco Pio, additional, Di Liberto, Diana, additional, de la Fuente, José, additional, and Sireci, Guido, additional
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- 2020
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17. Innate Immune Response to Tick-Borne Pathogens: Cellular and Molecular Mechanisms Induced in the Hosts
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Torina, Alessandra, primary, Villari, Sara, additional, Blanda, Valeria, additional, Vullo, Stefano, additional, La Manna, Marco Pio, additional, Shekarkar Azgomi, Mojtaba, additional, Di Liberto, Diana, additional, de la Fuente, José, additional, and Sireci, Guido, additional
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- 2020
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18. HLA-E–restricted CD8+ T Lymphocytes Efficiently Control Mycobacterium tuberculosis and HIV-1 Coinfection
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La Manna, Marco Pio, primary, Orlando, Valentina, additional, Prezzemolo, Teresa, additional, Di Carlo, Paola, additional, Cascio, Antonio, additional, Delogu, Giovanni, additional, Poli, Guido, additional, Sullivan, Lucy C., additional, Brooks, Andrew G., additional, Dieli, Francesco, additional, and Caccamo, Nadia, additional
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- 2020
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19. Mycobacterium tuberculosis Drives Expansion of Low-Density Neutrophils Equipped With Regulatory Activities
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La Manna, Marco Pio, primary, Orlando, Valentina, additional, Paraboschi, Elvezia Maria, additional, Tamburini, Bartolo, additional, Di Carlo, Paola, additional, Cascio, Antonio, additional, Asselta, Rosanna, additional, Dieli, Francesco, additional, and Caccamo, Nadia, additional
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- 2019
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20. Evaluation of Bone Marrow CD8+ tissue-Resident Memory T Cells in Multiple Myeloma
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Carlisi, Melania, primary, Mancuso, Salvatrice, additional, La Manna, Marco Pio, additional, Orlando, Valentina, additional, Caccamo, Nadia, additional, and Siragusa, Sergio, additional
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- 2019
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21. HLA-E–restricted CD8+ T Lymphocytes Efficiently Control Mycobacterium tuberculosis and HIV-1 Coinfection.
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La Manna, Marco Pio, Orlando, Valentina, Prezzemolo, Teresa, Carlo, Paola Di, Cascio, Antonio, Delogu, Giovanni, Poli, Guido, Sullivan, Lucy C., Brooks, Andrew G., Dieli, Francesco, and Caccamo, Nadia
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HLA histocompatibility antigens ,CD8 antigen ,MYCOBACTERIUM tuberculosis ,HIV infections ,TETRAMERS (Oligomers) - Abstract
We investigated the contribution of human leukocyte antigen A2 (HLA-A2) and HLA-E–restricted CD8
+ T cells in patients with Mycobacterium tuberculosis and human immunodeficiency virus 1 (HIV-1) coinfection. HIV-1 downregulates HLA-A, -B, and -C molecules in infected cells, thus influencing recognition by HLA class I–restricted CD8+ T cells but not by HLA-E–restricted CD8+ T cells, owing to the inability of the virus to downmodulate their expression. Therefore, antigen-specific HLA-E–restricted CD8+ T cells could play a protective role in Mycobacterium tuberculosis and HIV-1 coinfection. HLA-E– and HLA-A2–restricted Mycobacterium tuberculosis–specific CD8+ T cells were tested in vitro for cytotoxic and microbicidal activities, and their frequencies and phenotypes were evaluated ex vivo in patients with active tuberculosis and concomitant HIV-1 infection. HIV-1 and Mycobacterium tuberculosis coinfection caused downmodulation of HLA-A2 expression in human monocyte–derived macrophages associated with resistance to lysis by HLA-A2–restricted CD8+ T cells and failure to restrict the growth of intracellular Mycobacterium tuberculosis. Conversely, HLA-E surface expression and HLA-E–restricted cytolytic and microbicidal CD8 responses were not affected. HLA-E–restricted and Mycobacterium tuberculosis–specific CD8+ T cells were expanded in the circulation of patients with Mycobacterium tuberculosis/HIV-1 coinfection, as measured by tetramer staining, but displayed a terminally differentiated and exhausted phenotype that was rescued in vitro by anti–PD-1 (programmed cell death protein 1) monoclonal antibody. Together, these results indicate that HLA-E–restricted and Mycobacterium tuberculosis–specific CD8+ T cells in patients with Mycobacterium tuberculosis/HIV-1 coinfection have an exhausted phenotype and fail to expand in vitro in response to antigen stimulation, which can be restored by blocking the PD-1 pathway using the specific monoclonal antibody nivolumab. [ABSTRACT FROM AUTHOR]- Published
- 2020
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22. Identification of plasma biomarkers for discrimination between tuberculosis infection/disease and pulmonary non tuberculosis disease
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La Manna, Marco Pio, primary, Orlando, Valentina, additional, Li Donni, Paolo, additional, Sireci, Guido, additional, Di Carlo, Paola, additional, Cascio, Antonio, additional, Dieli, Francesco, additional, and Caccamo, Nadia, additional
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- 2018
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23. MONOCYTES MACROPHAGES EXPRESSION OF Ml OR M2 PHENOTYPES IN LATENT TUBERCULOSIS, ACTIVE DISEASES AND UNINFECTED MIGRANTS AND SICILIAN PATIENTS
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La Manna, Marco Pio, Paola Di Carlo, Claudia Colomba, Tumminia, S., Pasquale, Q., Carmela, Z., Adriana, C., Alice, M., Mililli, D., Guadagnino, G., Antonio Cascio, Caccamo, Nadia Rosalia, LA MANNA, M., DI CARLO, P., Colomba, C., Tumminia, S., Pasquale, Q., Carmela, Z., Adriana, C., Alice, M., Mililli, D., Guadagnino, G., Cascio, A., and Caccamo, N.
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MONOCYTES, Ml OR M2 PHENOTYPES, TUBERCULOSIS - Abstract
The high grade ofphenotype plasticity of monocytes macrophages, is resumed in two different cell subsets named M1 or M2. Several studies of microbial infections in vitro and in vivo, showed that, during the early stage of infection, macrophages are polarized toward Ml phenotype that should be protective against pathogen, while during the chronic phase of infection/disease macrophages polarize toward M2 phenotype to avoid damages from a prolonged Ml type activation.Obiettivo: In order to investigate if Mycobacterium tuberculosis infection can drive circulating monocytes toward the expression of Ml or M2 phenotypes, we have analyzed by flow cytometry monocytes obtained from patients with active tuberculosis (TB) at early phase of disease and during anti mycobacterial therapy, subjects with latent TB and healthy uninfected control. Risultatil Analysis of surface markers expression showed no clearcut Ml/M2 polarization in all tested groups, but we found a very high percentage of RANK+ monocytes in patients with active TB disease before treatment, while RANK expression was very faint in monocytes from all other experimental groups. Moreover the statistical analysis of geometric MFI of RANK showed a signifìcant difference between patients with active disease compared to all the others groups. Conclusioni: Given that the available in vitro diagnostic tests are limited in discriminating subjects with latent or active disease, as well as response to therapy,,we speculate that the evaluation of RANK expression on monocytes could represent an additional biomarker useful to support diagnosis of active disease and monitor the response to therapy.
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- 2016
24. Quantitative and qualitative profiles of circulating monocytes may help identifying tuberculosis infection and disease stages
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La Manna, Marco Pio, primary, Orlando, Valentina, additional, Dieli, Francesco, additional, Di Carlo, Paola, additional, Cascio, Antonio, additional, Cuzzi, Gilda, additional, Palmieri, Fabrizio, additional, Goletti, Delia, additional, and Caccamo, Nadia, additional
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- 2017
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25. Preliminary results of EOLIFE99, a project concerning the conservation of four endangered plant species of Aeolian Archipelago (South Tyrrhenian Sea, Italy)
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TROIA, Angelo, CARDINALE, Massimiliano, LA MANNA, Marco Pio, PUGLIA, Anna Maria, QUATRINI, Paola, LO CASCIO P, PASTA S, VOUTSINAS E., Troia, Angelo, Cardinale, Massimiliano, La Manna, Marco Pio, Lo Cascio, Pietro, Pasta, Salvatore, Puglia, Anna Maria, Quatrini, Paola, Voutsinas, Emanuela, TROIA A, CARDINALE M, LA MANNA M, LO CASCIO P, PASTA S, PUGLIA AM, QUATRINI P, and VOUTSINAS E
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con ervation, endangered plants, Aeolian Islands - Published
- 2005
26. Heterogeneity and prognostic influence of tumor-infiltrating gamma-delta T lymphocytes in colon cancer patients
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Dieli Francesco, Caccamo Nadia, Cutrera Stella, Di Liberto Diana, La Manna Marco Pio, Buccheri Simona, Orlando Valentina, Cicero Giuseppe, Meraviglia Serena, Lo Presti Elena, Lo Presti, E, Meraviglia, S, Cicero, G, Orlando, V, Buccheri, S, La Manna, MP, Di Liberto, D, Cutrera, S, Caccamo, N, and Dieli, F
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gamma-delta T cells, Colon Cancer, immunosurveillance, Immunotherapy, tumor immunity ,business.industry ,Colorectal cancer ,Immunology ,Cancer research ,Medicine ,Immunology and Allergy ,business ,medicine.disease - Published
- 2013
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27. The Janus Face of NKT Cell Function in Autoimmunity and Infectious Diseases.
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Torina, Alessandra, Guggino, Giuliana, La Manna, Marco Pio, and Sireci, Guido
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KILLER cells ,T cells ,AUTOIMMUNITY ,SULFATIDES ,GLYCOLIPIDS ,ENDOPLASMIC reticulum - Abstract
Natural killer T cells (NKT) are a subset of T lymphocytes bridging innate and adaptive immunity. These cells recognize self and microbial glycolipids bound to non-polymorphic and highly conserved CD1d molecules. Three NKT cell subsets, type I, II, and NKT-like expressing different antigen receptors (TCR) were described and TCR activation promotes intracellular events leading to specific functional activities. NKT can exhibit different functions depending on the secretion of soluble molecules and the interaction with other cell types. NKT cells act as regulatory cells in the defense against infections but, on the other hand, their effector functions can be involved in the pathogenesis of several inflammatory disorders due to their exposure to different microbial or self-antigens, respectively. A deep understanding of the biology and functions of type I, II, and NKT-like cells as well as their interplay with cell types acting in innate (neuthrophils, innate lymphoid cells, machrophages, and dendritic cells) and adaptive immunity (CD4
+ ,CD8+ , and double negative T cells) should be important to design potential immunotherapies for infectious and autoimmune diseases. [ABSTRACT FROM AUTHOR]- Published
- 2018
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28. Antigen-Specific T Cells and Cytokines Detection as Useful Tool for Understanding Immunity against Zoonotic Infections
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Agnone, Annalisa, Torina, Alessandra, Vesco, Gesualdo, Villari, Sara, Vitale, Fabrizio, Caracappa, Santo, La Manna, Marco Pio, Dieli, Francesco, and Sireci, Guido
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Article Subject - Abstract
Zoonoses include a broad range of diseases, that are becoming of great interest, due to the climate changing, that cause the adaptation of vectors to new niches and environments. Host immune responses play a crucial role in determining the outcome of infections, as documented by expansion of antigen-specific T cells during several zoonotic infections. Thus, understanding of the contribution of antigen-specific T-cell subsets in the host immune response is a powerful tool to evaluate the different immunological mechanisms involved in zoonotic infections and for the development of effective vaccines. In this paper we discuss the role of T cells in some eukaryotic and prokaryotic infectious models.
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- 2012
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29. Functional Signatures of Human CD4 and CD8 T Cell Responses to Mycobacterium tuberculosis
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Prezzemolo, Teresa, primary, Guggino, Giuliana, additional, La Manna, Marco Pio, additional, Di Liberto, Diana, additional, Dieli, Francesco, additional, and Caccamo, Nadia, additional
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- 2014
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30. Prophylaxis of lipopolysaccharide-induced shock by α-galactosylceramide
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Sireci, Guido, primary, La Manna, Marco Pio, additional, Di Liberto, Diana, additional, Lo Dico, Marco, additional, Taniguchi, Masaru, additional, Dieli, Francesco, additional, and Salerno, Alfredo, additional
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- 2008
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31. Anti-16-Kilodalton Mycobacterial Protein Immunoglobulin M Levels in Healthy but Purified Protein Derivative-Reactive Children Decrease after Chemoprophylaxis
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Sireci, Guido, primary, Dieli, Francesco, additional, Di Liberto, Diana, additional, Buccheri, Simona, additional, La Manna, Marco Pio, additional, Scarpa, Francesco, additional, Macaluso, Pasquale, additional, Romano, Amelia, additional, Titone, Lucina, additional, Di Carlo, Paola, additional, Singh, Mahavir, additional, Ivanyi, Jurayi, additional, and Salerno, Alfredo, additional
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- 2007
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32. ESAT-6 Peptide Recognition by Bovine CD8 + Lymphocytes of Naturally Infected Cows in Herds from Southern Italy
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Vitale, Fabrizio, primary, Reale, Stefano, additional, Petrotta, Enrico, additional, Caracappa, Santo, additional, Barera, Annalisa, additional, La Manna, Marco Pio, additional, Macaluso, Pasquale, additional, Caccamo, Nadia, additional, Dieli, Francesco, additional, Vordermeier, Hans Martin, additional, Sireci, Guido, additional, and Salerno, Alfredo, additional
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- 2006
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33. Functional signatures of human CD4 and CD8T cell responses to Mycobacterium tuberculosis.
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Prezzemolo, Teresa, Guggino, Giuliana, La Manna, Marco Pio, Di Liberto, Diana, Dieli, Francesco, and Caccamo, Nadia
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CD4 antigen ,MYCOBACTERIUM tuberculosis ,COMMUNICABLE diseases ,DRUG resistance ,CYTOKINES ,T cells ,IMMUNODEFICIENCY - Abstract
With 1.4 million deaths and 8.7 million new cases in 2011, tuberculosis (TB) remains a global health care problem and together with HIV and Malaria represents one of the three infectious diseases world-wide. Control of the global TB epidemic has been impaired by the lack of an effective vaccine, by the emergence of drug-resistant forms of Mycobacterium tuberculosis (Mtb) and by the lack of sensitive and rapid diagnostics. It is estimated, by epidemiological reports, that one third of the world's population is latently infected with Mtb, but the majority of infected individuals develop long-lived protective immunity, which controls and contains Mtb in a T cell-dependent manner. Development of TB disease results from interactions among the environment, the host, and the pathogen, and known risk factors include HIV co-infection, immunodeficiency, diabetes mellitus, overcrowding, malnutrition, and general poverty; therefore, an effective T cell response determines whether the infection resolves or develops into clinically evident disease. Consequently, there is great interest in determining which T cells subsets mediate anti-mycobacterial immunity, delineating their effector functions. On the other hand, many aspects remain unsolved in understanding why some individuals are protected from Mtb infection while others go on to develop disease. Several studies have demonstrated that CD4
+ T cells are involved in protection against Mtb, as supported by the evidence that CD4+ T cell depletion is responsible for Mtb reactivation in HIV-infected individuals. There are many subsets of CD4+ T cells, such as T-helper 1 (Th1), Th2, Th17, and regulatory T cells (Tregs), and all these subsets cooperate or interfere with each other to control infection; the dominant subset may differ between active and latent Mtb infection cases. Mtb-specific-CD4+ Th1 cell response is considered to have a protective role for the ability to produce cytokines such as IFN-γ or TNF-α that contribute to the recruitment and activation of innate immune cells, like monocytes and granulocytes. Thus, while other antigen (Ag)-specific T cells such as CD8+ T cells, natural killer (NK) cells, γδ T cells, and CD1-restricted T cells can also produce IFN-γ during Mtb infection, they cannot compensate for the lack of CD4+ T cells. The detection of Ag-specific cytokine production by intracellular cytokine staining (ICS) and the use of flow cytometry techniques are a common routine that supports the studies aimed at focusing the role of the immune system in infectious diseases. Flow cytometry permits to evaluate simultaneously the presence of different cytokines that can delineate different subsets of cells as having "multifunctional/polyfunctional" profile. It has been proposed that polyfunctional T cells, are associated with protective immunity toward Mtb, in particular it has been highlighted that the number of Mtb-specific T cells producing a combination of IFN-γ, IL-2, and/or TNF-α may be correlated with themycobacterial load, while other studies have associated the presence of this particular functional profile as marker of TB disease activity. Although the role of CD8T cells in TB is less clear than CD4 T cells, they are generally considered to contribute to optimal immunity and protection. CD8T cells possess a number of anti-microbial effector mechanisms that are less prominent or absent in CD4 Th1 and Th17 T cells. The interest in studying CD8T cells that are either MHC-class Ia or MHC-class Ib-restricted, has gained more attention. These studies include the role of HLA-E-restricted cells, lung mucosal-associated invariant T-cells (MAIT), and CD1-restricted cells. Nevertheless, the knowledge about the role of CD8+ T cells in Mtb infection is relatively new and recent studies have delineated that CD8 T cells, which display a functional profile termed "multifunctional," can be a better marker of protection inTB than CD4+ T cells. Their effector mechanisms could contribute to control Mtb infection, as upon activation, CD8 T cells release cytokines or cytotoxic molecules, which cause apoptosis of target cells. Taken together, the balance of the immune response in the control of infection and possibly bacterial eradication is important in understanding whether the host immune response will be appropriate in contrasting the infection or not, and, consequently, the inability of the immune response, will determine the dissemination and the transmission of bacilli to new subjects. In conclusion, the recent highlights on the role of different functional signatures of T cell subsets in the immune response toward Mtb infection will be discerned in this review, in order to summarize what is known about the immune response in human TB. In particular, we will discuss the role of CD4 and CD8T cells in contrasting the advance of the intracellular pathogen in already infected people or the progression to active disease in subjects with latent infection. All the information will be aimed at increasing the knowledge of this complex disease in order to improve diagnosis, prognosis, drug treatment, and vaccination. [ABSTRACT FROM AUTHOR]- Published
- 2014
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34. A Rapid and Simple Multiparameter Assay to Quantify Spike-Specific CD4 and CD8 T Cells after SARS-CoV-2 Vaccination: A Preliminary Report.
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Azgomi, Mojtaba Shekarkar, La Manna, Marco Pio, Badami, Giusto Davide, Ragonese, Paolo, Trizzino, Antonino, Dieli, Francesco, and Caccamo, Nadia
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T cells ,SARS-CoV-2 ,CD8 antigen ,CD4 antigen ,IMMUNOLOGIC memory - Abstract
mRNA and Adenovirus vaccines for COVID-19 are used to induce humoral and cell-mediated immunity, with the aim to generate both SARS-CoV-2 B and T memory cells. In present study, we described a simple assay to detect and quantify Spike-specific CD4
+ and CD8+ T cell responses induced by vaccination in healthy donors and in subjects with B cell compart impairment, in which antibody response is absent due to primary immunodeficiencies or CD20 depleting therapy. We detect and quantified memory T cell immune responses against SARS-CoV-2 evocated by vaccination in both groups, irrespective to the humoral response. Furthermore, we identified TNF-α as the main cytokine produced by T memory cells, after antigen-specific stimulation in vitro, that could be considered, other than IFN-γ, an additional biomarker of induction of T memory cells upon vaccination. Further studies on the vaccine-induced T cell responses could be crucial, not only in healthy people but also in immunocompromised subjects, where antigen specific T cells responses play a protective role against SARS-CoV-2. [ABSTRACT FROM AUTHOR]- Published
- 2021
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35. ESAT-6 Peptide Recognition by Bovine CD8+Lymphocytes of Naturally Infected Cows in Herds from Southern Italy
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Vitale, Fabrizio, Reale, Stefano, Petrotta, Enrico, Caracappa, Santo, Barera, Annalisa, La Manna, Marco Pio, Macaluso, Pasquale, Caccamo, Nadia, Dieli, Francesco, Vordermeier, Hans Martin, Sireci, Guido, and Salerno, Alfredo
- Abstract
ABSTRACTThe aim of this study was to define epitopes of Mycobacterium bovisfrom ESAT-6 (early secretory antigen of 6 kDa) recognized by CD8+T lymphocytes from cows naturally infected with Mycobacterium bovis. We found that bovine CD8+T cells recognized 10 out of 11 ESAT-6 peptides tested.
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- 2006
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36. ESAT-6 Peptide Recognition by Bovine CD8+ Lymphocytes of Naturally Infected Cows in Herds from Southern Italy
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Vitale, Fabrizio, Reale, Stefano, Petrotta, Enrico, Caracappa, Santo, Barera, Annalisa, La Manna, Marco Pio, Macaluso, Pasquale, Caccamo, Nadia, Dieli, Francesco, Vordermeier, Hans Martin, Sireci, Guido, and Salerno, Alfredo
- Abstract
The aim of this study was to define epitopes of Mycobacterium bovis from ESAT-6 (early secretory antigen of 6 kDa) recognized by CD8+ T lymphocytes from cows naturally infected with Mycobacterium bovis. We found that bovine CD8+ T cells recognized 10 out of 11 ESAT-6 peptides tested.
- Published
- 2006
37. Evaluation of Bone Marrow CD8+tissue-Resident Memory T Cells in Multiple Myeloma
- Author
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Carlisi, Melania, Mancuso, Salvatrice, La Manna, Marco Pio, Orlando, Valentina, Caccamo, Nadia, and Siragusa, Sergio
- Abstract
Background: CD8+T cell responses are an essential component of the adaptive immune system. After resolution of infection a small population of memory cells is formed. In relation to circulatory patterns, different subsets of memory CD8+T cells can be identified: the central memory (CM) and the effector memory T cells (EM) (Martin MD, et al., Front Immunol. 2018). In addition, it has been described a subset of resident memory T cells (TRM) permanently living in peripheral tissues, including the bone marrow (BM) (Di Rosa F., et al., Nat Rev Immunol. 2016). It is conceivable that these cells can contribute to the defence toward haematological tumours infiltrating the BM. Therefore, we performed a study to evaluate the frequency and the phenotype of BM CD8+TRMin patients with multiple myeloma (MM). Moreover, to evaluate the contribution that the microenvironment can have on the homeostatic and functional maintenance of these cells, we performed in vitroexperiments of BM-derived mononucleate cells of MM patients cultured in the presence of different homeostatic cytokines.
- Published
- 2019
- Full Text
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38. B-Cell Receptor Signaling Is Thought to Be a Bridge between Primary Sjogren Syndrome and Diffuse Large B-Cell Lymphoma
- Author
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Leila Mohammadnezhad, Mojtaba Shekarkar Azgomi, Marco Pio La Manna, Giuliana Guggino, Cirino Botta, Francesco Dieli, Nadia Caccamo, Mohammadnezhad, Leila, Shekarkar Azgomi, Mojtaba, La Manna, Marco Pio, Guggino, Giuliana, Botta, Cirino, Dieli, Francesco, and Caccamo, Nadia
- Subjects
non-hodgkins lymphoma ,primary Sjogren syndrome ,DLBCL ,cell signaling ,BCR ,Organic Chemistry ,General Medicine ,Catalysis ,Computer Science Applications ,Inorganic Chemistry ,Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy - Abstract
Primary Sjogren syndrome (pSS) is the second most common autoimmune disorder worldwide, which, in the worst scenario, progresses to Non-Hodgkin Lymphoma (NHL). Despite extensive studies, there is still a lack of knowledge about developing pSS for NHL. This study focused on cells’ signaling in pSS progression to the NHL type of diffuse large B-cell lymphoma (DLBCL). Using bulk RNA and single cell analysis, we found five novel pathologic-independent clusters in DLBCL based on cells’ signaling. B-cell receptor (BCR) signaling was identified as the only enriched signal in DLBCL and pSS peripheral naive B-cells or salivary gland-infiltrated cells. The evaluation of the genes in association with BCR has revealed that targeting CD79A, CD79B, and LAMTOR4 as the shared genes can provide novel biomarkers for pSS progression into lymphoma.
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- 2023
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39. Interleukin-6 Is a Promising Marker of COVID-19 in Children: A Case Series of 2 Brothers with Severe COVID-19 Pneumonia
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Maria Cristina Maggio, Maria Concetta Failla, Salvatore Giordano, Marco Pio La Manna, Guido Sireci, Maggio, Maria Cristina, Failla, Maria Concetta, Giordano, Salvatore, La Manna, Marco Pio, and Sireci, Guido
- Subjects
Settore MED/04 - Patologia Generale ,Male ,Fever ,Interleukin-6 ,SARS-CoV-2 ,Siblings ,COVID-19 ,Infant ,General Medicine ,Pneumonia ,Methylprednisolone ,Settore MED/38 - Pediatria Generale E Specialistica ,Cough ,Humans ,Pandemics ,Aged - Abstract
BACKGROUND To date, Coronavirus disease 2019 (COVID-19) remains a global health concern, with fatalities mostly in older age groups with underlying medical conditions, while children are less likely to manifest severe symptoms. CASE REPORT We describe the clinical cases of 2 brothers admitted to our Children's Hospital for persistent fever and cough during the COVID-19 pandemic. Case 1. A 1.5-year-old boy had fever, expiratory dyspnea, desaturation, oxygen saturation 94-96% with O2, and bilateral hissing and crackling rales. His interleukin-6 level in the acute phase of the disease was 100.41 and at the resolution it was 46.2 pg/ml. Treatment with amoxicillin plus clavulanic acid, methylprednisolone, and O2 allowed progressive improvement of clinical conditions and laboratory data. Case 2. A 3-month-old toddler was admitted to our hospital for fever, cough, and tachypnea, which started 2 days before hospitalization. He had fever, cough, conjunctivitis, mucous rhinorrhea, and 99% oxygen saturation on room air. Thorax auscultation showed whistles and buzzes. He had a positive molecular test result from a COVID-19 swab. Interleukin-6 levels during all the phases of the disease were
- Published
- 2022
40. Phenotypic and Immunometabolic Aspects on Stem Cell Memory and Resident Memory CD8+ T Cells
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Marco Pio La Manna, Mojtaba Shekarkar Azgomi, Bartolo Tamburini, Giusto Davide Badami, Leila Mohammadnezhad, Francesco Dieli, Nadia Caccamo, La Manna, Marco Pio, Shekarkar Azgomi, Mojtaba, Tamburini, Bartolo, Badami, Giusto Davide, Mohammadnezhad, Leila, Dieli, Francesco, and Caccamo, Nadia
- Subjects
Settore MED/04 - Patologia Generale ,Memory T Cells ,Phenotype ,Stem Cells ,Immunology ,Immunology and Allergy ,CD8-Positive T-Lymphocytes ,infectious diseases ,Immunologic Memory ,CD8 TRM cells ,CD8 TSCM cells - Abstract
The immune system, smartly and surprisingly, saves the exposure of a particular pathogen in its memory and reacts to the pathogen very rapidly, preventing serious diseases.Immunologists have long been fascinated by understanding the ability to recall and respond faster and more vigorously to a pathogen, known as “memory”.T-cell populations can be better described by using more sophisticated techniques to define phenotype, transcriptional and epigenetic signatures and metabolic pathways (single-cell resolution), which uncovered the heterogeneity of the memory T-compartment. Phenotype, effector functions, maintenance, and metabolic pathways help identify these different subsets. Here, we examine recent developments in the characterization of the heterogeneity of the memory T cell compartment. In particular, we focus on the emerging role of CD8+TRMand TSCMcells, providing evidence on how their immunometabolism or modulation can play a vital role in their generation and maintenance in chronic conditions such as infections or autoimmune diseases.
- Published
- 2022
41. Impact of antiretroviral and tuberculosis therapies on CD4 + and CD8 + HIV/M. tuberculosis-specific T-cell in co-infected subjects
- Author
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Elisa Petruccioli, Teresa Chiacchio, Carmela Pinnetti, Valentina Orlando, Valentina Vanini, Gilda Cuzzi, Delia Goletti, Nadia Caccamo, Marco Pio La Manna, Andrea Antinori, Alessandro Sampaolesi, Chiacchio, Teresa, Petruccioli, Elisa, Vanini, Valentina, Cuzzi, Gilda, La Manna, Marco Pio, Orlando, Valentina, Pinnetti, Carmela, Sampaolesi, Alessandro, Antinori, Andrea, Caccamo, Nadia, and Goletti, Delia
- Subjects
Adult ,Male ,0301 basic medicine ,Tuberculosis ,Tuberculosi ,Immunology ,T-Lymphocyte Subset ,Mycobacterium tuberculosi ,Peripheral blood mononuclear cell ,Mycobacterium tuberculosis ,Antitubercular Agent ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,Immunology and Allergy ,Medicine ,HIV Infection ,030212 general & internal medicine ,CD8 + T-cells ,Risk factor ,Cytokine ,HIV Antigen ,Antigens, Bacterial ,biology ,Coinfection ,business.industry ,HIV ,virus diseases ,CD8-Positive T-Lymphocyte ,bacterial infections and mycoses ,medicine.disease ,biology.organism_classification ,030104 developmental biology ,HIV Antigens ,CD4-Positive T-Lymphocyte ,CD4 + T-cells ,Tuberculosis therapy ,Leukocytes, Mononuclear ,Anti-Retroviral Agent ,Female ,business ,ART ,CD8 ,Human - Abstract
Background Human Immunodeficiency Virus (HIV) infection is a risk factor for tuberculosis (TB). Antiretroviral therapy (ART) changed HIV clinical management but it is still unclear how pre-existing HIV/Mycobacterium tuberculosis (Mtb)-specific CD4+ and CD8+ T-cells are restored. Aim to evaluate the impact of ART and TB therapies on the functional and phenotypic profile of Mtb-specific antigen-response of CD4+ and CD8+ T-cells in prospectively enrolled HIV-TB co-infected patients. Methods ART-naive HIV-infected patients, with or without active TB or latent TB infection (LTBI), were enrolled before and after starting ART and TB therapies. Peripheral blood mononuclear cells (PBMC) were stimulated overnight with Mtb and HIV antigens (GAG). Cytokine expression and phenotype profile were evaluated by flow cytometry. Cytomegalovirus (CMV) and staphylococcal enterotoxin B (SEB) were also used. Results The median of absolute number of CD4+ T-cells increased after ART and TB therapies in all groups analyzed, while the median of absolute number of CD8+ T-cells decreases in HIV and HIV-LTBI groups. Treatments significantly increased the frequency of Mtb-specific CD4+ T-cells in the HIV-LTBI (p = 0.015) with a rise of the central memory compartment. The magnitude of the CD4+ T-cell response to HIV-GAG significantly increased in active TB (p = 0.03), whereas the magnitude of CMV-specific CD4+ T-cell response decreased in all the groups. Similarly, the treatments increased the number of Mtb-specific CD8+ responders in both HIV-LTBI and HIV-TB groups, whereas the phenotype distribution was dependent on the antigens used and on the stage of infection/disease. Conclusions After therapies the median of absolute number and the proportion of CD4+ T-cells increased in all groups whereas the median of absolute count and proportion of CD8+ T-cells decreased in the HIV and HIV-LTBI subjects. Interestingly, an increased frequency of CD4+ T-cell response to RD1 proteins in HIV-LTBI subjects was found. These results contribute to a better understanding of the effect of ART and TB therapies on the modulation of Mtb-specific CD4+ and CD8+ T-cells subsets.
- Published
- 2018
42. Tumor-Derived Small Extracellular Vesicles Induce Pro-Inflammatory Cytokine Expression and PD-L1 Regulation in M0 Macrophages via IL-6/STAT3 and TLR4 Signaling Pathways
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Ornella Urzì, Alice Conigliaro, Marco Pio La Manna, Riccardo Alessandro, Nadia Caccamo, Maria Antonietta Di Bella, Marzia Pucci, Stefania Raimondo, Marta Moschetti, Simona Fontana, Pucci, Marzia, Raimondo, Stefania, Urzì, Ornella, Moschetti, Marta, Di Bella, Maria Antonietta, Conigliaro, Alice, Caccamo, Nadia, La Manna, Marco Pio, Fontana, Simona, and Alessandro, Riccardo
- Subjects
STAT3 Transcription Factor ,PD-L1 ,QH301-705.5 ,colorectal cancer ,small extracellular vesicles ,B7-H1 Antigen ,Article ,Catalysis ,Stat3 Signaling Pathway ,Proinflammatory cytokine ,M0 macrophage ,Inorganic Chemistry ,Extracellular Vesicles ,Settore BIO/13 - Biologia Applicata ,Cell Line, Tumor ,Tumor-Associated Macrophages ,small extracellular vesicle ,Humans ,Macrophage ,TLR4 ,Biology (General) ,Physical and Theoretical Chemistry ,M0 macrophages ,QD1-999 ,Molecular Biology ,Spectroscopy ,Inflammation ,Tumor microenvironment ,biology ,Interleukin-6 ,Chemistry ,Organic Chemistry ,General Medicine ,Computer Science Applications ,Gene Expression Regulation, Neoplastic ,Toll-Like Receptor 4 ,multiple myeloma ,Cell culture ,Tumor progression ,Colonic Neoplasms ,biology.protein ,Cancer research ,Signal Transduction - Abstract
Tumor-associated macrophages play a key role in promoting tumor progression by exerting an immunosuppressive phenotype associated with the expression of programmed cell death ligand 1 (PD-L1). It is well known that tumor-derived small extracellular vesicles (SEVs) affect the tumor microenvironment, influencing TAM behavior. The present study aimed to examine the effect of SEVs derived from colon cancer and multiple myeloma cells on macrophage functions. Non-polarized macrophages (M0) differentiated from THP-1 cells were co-cultured with SEVs derived from a colorectal cancer (CRC) cell line, SW480, and a multiple myeloma (MM) cell line, MM1.S. The expression of PD-L1, interleukin-6 (IL-6), and other inflammatory cytokines as well as of the underlying molecular mechanisms were evaluated. Our results indicate that SEVs can significantly upregulate the expressions of PD-L1 and IL-6 at both the mRNA and protein levels and can activate the STAT3 signaling pathway. Furthermore, we identified the TLR4/NF-kB pathway as a convergent mechanism for SEV-mediated PD-L1 expression. Overall, these preliminary data suggest that SEVs contribute to the formation of an immunosuppressive microenvironment.
- Published
- 2021
43. Evaluation of Bone Marrow CD8+ tissue-Resident Memory T Cells in Multiple Myeloma
- Author
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Marco Pio La Manna, Salvatrice Mancuso, Sergio Siragusa, Melania Carlisi, Nadia Caccamo, Valentina Orlando, Carlisi, Melania, Mancuso, Salvatrice, La Manna, Marco Pio, Orlando, Valentina, Caccamo, Nadia, and Siragusa, Sergio
- Subjects
education.field_of_study ,medicine.medical_treatment ,T cell ,CD3 ,Immunology ,Population ,Cell Biology ,Hematology ,Biology ,Biochemistry ,Molecular biology ,Settore MED/15 - Malattie Del Sangue ,Cytokine ,medicine.anatomical_structure ,bone marrow, multiple myeloma, t-lymphocytes, memory, cytokine, interleukin-15, interleukin-7, cd45 antigens, immunoglobulin a, immunoglobulin g, ki-67 antigen ,Interleukin 15 ,medicine ,biology.protein ,Cytotoxic T cell ,Bone marrow ,education ,CD8 - Abstract
Background: CD8+ T cell responses are an essential component of the adaptive immune system. After resolution of infection a small population of memory cells is formed. In relation to circulatory patterns, different subsets of memory CD8+ T cells can be identified: the central memory (CM) and the effector memory T cells (EM) (Martin MD, et al., Front Immunol. 2018). In addition, it has been described a subset of resident memory T cells (TRM) permanently living in peripheral tissues, including the bone marrow (BM) (Di Rosa F., et al., Nat Rev Immunol. 2016). It is conceivable that these cells can contribute to the defence toward haematological tumours infiltrating the BM. Therefore, we performed a study to evaluate the frequency and the phenotype of BM CD8+ TRM in patients with multiple myeloma (MM). Moreover, to evaluate the contribution that the microenvironment can have on the homeostatic and functional maintenance of these cells, we performed in vitro experiments of BM-derived mononucleate cells of MM patients cultured in the presence of different homeostatic cytokines. Patients and Methods: we prospectively analysed 21 patients, 16 with a new diagnosis of IgA, IgG and light chain multiple myeloma (MM) and 5 with IgA and IgG smoldering myeloma (SM). At the time of the bone marrow assessment, we collected a sample for the flow cytometry analysis and in vitro cell culture. The ex vivo evaluation of CD8+ TRM frequency and phenotype in BM samples was performed using anti-human mAbs to CD3, CD103, CD69, CD45, CD8, CD45RA and CCR7 (CD197). The sequential gating strategy was: gate on lymphocytes population with CD45 vs. SSC, 7AAD negative cells, exclusion of doublets with FSC-H vs. FSC-A, CD8+CD3+ and evaluation of percentage of CD103+CD69+ cells. Was also established the subsets using CCR7 and CD45RA. Moreover, to evaluate the role of the microenvironment on maintenance of these cells, we performed in vitro experiments of BM-derived mononucleate cells of MM patients cultured in the presence of homeostatic cytokines in maintaining these cells for a long time. BM derived mononucleate cells from patients were then cultured in vitro in complete RPMI with 10% of human serum for 4 days with IL15 (25 ng/ml), IL7 (25 ng/ml) and TGF-β (2 ng/ml), in different combination and in RPMI alone. After culture, we analyzed the frequency of CD8+ TRM and the proliferating fraction with intracellular staining with anti human Ki67 APC. Non parametric Mann-Whitney and Kruskall-wallis tests were performed to determine statistical differences in the distribution of the results using GraphPad Prism 7.00. Values of * p Results: the ex vivo average frequency of CD8+ TRM in 16 MM patients was of 0.48% and the phenotype was represented mainly by TEM (72,9%) followed by TEMRA (12.3%) and (7,6%) of naïve cells and (7,2%) of TCM (Fig. A). The comparison with the ex vivo frequency of CD8 TRM in SM patients did not show any significant difference between two groups (data not showed). To evaluate factors capable of maintaining or to induce the expansion of these cells in vitro, we maintained BM-derived mononucleate cells from MM patients for 4 days in presence of homeostatic cytokines, IL-15, IL-7 plus IL-15 and IL-7 together with IL-15 and TGF-β. The result showed an increase of the percentage of CD8+ TRM in all conditions tested, especially in presence of all cytokines (Fig. B), with a percentage of CD8 TRM of 2,74%. Regarding the phenotype distribution, we observed an expansion of CM compared to the other subsets (Fig. C). We also analysed the percentage of CD8+ TRM proliferating through the identification of Ki67 positive cells. Data highlight that IL-15 gives the strongest proliferative input, but also other cytokines contribute to the homeostatic maintenance of these cells (Fig. D). Conclusions: we evaluated the frequency and the phenotype of CD8 TRM in BM of MM patients compared to SM patients with the conclusion that these cells do not differ significantly in percentage and phenotypic distribution in both conditions. In MM patients, the increase of CD8+ TRM cells with a CM phenotype after in vitro culture with the three cytokines could have an anti-tumor role in the control of MM. Further studies are needed to investigate the cytotoxic capacity of these cells against myeloma cells, in order to study their functional role, also in the perspective of a possible use in future therapeutic programs. Disclosures No relevant conflicts of interest to declare.
- Published
- 2019
44. The janus face of NKT cell function in autoimmunity and infectious diseases
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Giuliana Guggino, Alessandra Torina, Marco Pio La Manna, Guido Sireci, Torina, Alessandra, Guggino, Giuliana, La Manna, Marco Pio, and Sireci, Guido
- Subjects
0301 basic medicine ,glycolipids ,Autoimmunity ,Review ,Adaptive Immunity ,medicine.disease_cause ,Catalysi ,immunology ,lcsh:Chemistry ,0302 clinical medicine ,T-Lymphocyte Subsets ,lcsh:QH301-705.5 ,Spectroscopy ,Innate lymphoid cell ,hemic and immune systems ,Computer Science Applications1707 Computer Vision and Pattern Recognition ,General Medicine ,NKT ,Natural killer T cell ,Acquired immune system ,Computer Science Applications ,Cell biology ,CD1D ,microbes ,Cell type ,chemical and pharmacologic phenomena ,Glycolipid ,Biology ,CD1d ,Communicable Diseases ,Catalysis ,Inorganic Chemistry ,03 medical and health sciences ,medicine ,Animals ,Humans ,Microbe ,Physical and Theoretical Chemistry ,Molecular Biology ,Inflammation ,T-cell receptor ,Organic Chemistry ,Models, Immunological ,Alpha-galactosylceramide ,Glycolipids ,Microbes ,Sulfatide ,Immunity, Innate ,Settore MED/16 - Reumatologia ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,biology.protein ,Natural Killer T-Cells ,CD8 ,030215 immunology - Abstract
Natural killer T cells (NKT) are a subset of T lymphocytes bridging innate and adaptive immunity. These cells recognize self and microbial glycolipids bound to non-polymorphic and highly conserved CD1d molecules. Three NKT cell subsets, type I, II and NKT-like expressing different antigen receptors (TCR) were described and TCR activation promotes intracellular events leading to specific functional activities. NKT can exhibit different functions depending on the secretion of soluble molecules and the interaction with other cell types. NKT cells act as regulatory cells in the defence against infections but, on the other hand, their effector functions can be involved in the pathogenesis of several inflammatory disorders due to their exposure to different microbial or self antigens, respectively. A deep understanding of the biology and functions of type I, II and NKT-like cells as well as their interplay with cell types acting in innate (Neuthrophils, Innate Lymphoid cells, Machrophages and Dendritic cells) and adaptive immunity (CD4+,CD8+ and Double Negative T cells) should be important to design potential immunotherapies for infectious and autoimmune diseases.
- Published
- 2018
45. Downregulation of miRNA17-92 cluster marks Vγ9Vδ2 T cells from patients with rheumatoid arthritis
- Author
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Laura Saieva, Marco Pio La Manna, Roberto Giacomelli, Francesco Ciccia, Valentina Orlando, Giuliana Guggino, Francesco Dieli, Giovanni Triolo, Riccardo Alessandro, Piero Ruscitti, Paola Cipriani, Nadia Caccamo, Guggino, Giuliana, Orlando, Valentina, Saieva, Laura, Ruscitti, Piero, Cipriani, Paola, La Manna, Marco Pio, Giacomelli, Roberto, Alessandro, Riccardo, Triolo, Giovanni, Ciccia, Francesco, Dieli, Francesco, Caccamo, Nadia, Guggino, G., Orlando, V., Saieva, L., Ruscitti, P., Cipriani, P., La Manna, M. P., Giacomelli, R., Alessandro, R., Triolo, G., Ciccia, F., Dieli, F., and Caccamo, N.
- Subjects
Adult ,Male ,0301 basic medicine ,miRNA17–92 ,lcsh:Diseases of the musculoskeletal system ,Inflammatory cytokine ,Immunology ,Down-Regulation ,Biology ,γδ T cells ,Proinflammatory cytokine ,Flow cytometry ,Arthritis, Rheumatoid ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Rheumatology ,T-Lymphocyte Subsets ,Inflammatory cytokines ,miRNA17-92 ,Rheumatoid arthritis ,Immunology and Allergy ,microRNA ,medicine ,Humans ,Rheumatoid arthriti ,γδ T cell ,medicine.diagnostic_test ,Effector ,Interleukin ,Middle Aged ,Phenotype ,MicroRNAs ,Settore MED/16 - Reumatologia ,030104 developmental biology ,030220 oncology & carcinogenesis ,Female ,lcsh:RC925-935 ,Research Article - Abstract
Background We aimed to evaluate the phenotype, function, and microRNA (miRNA)17–92 cluster expression in Vγ9Vδ2 T-cell subsets and the correlation with immune response in rheumatoid arthritis (RA) patients. Methods Peripheral blood from 10 early RA untreated patients and 10 healthy donors (HD) was obtained. Polyclonal Vγ9Vδ2 T-cell lines were generated and analysed by flow cytometry. Analysis of miRNA17–92 cluster expression was performed by real-time polymerase chain reaction (RT-PCR), and expression of mRNA target genes was also studied. Results A remarkable change in the distribution of Vγ9Vδ2 T-cell functional subsets was observed in the peripheral blood of RA patients compared with HD, with an expansion of effector subsets and reduction of naive cells which was accompanied by modifications in proinflammatory cytokine expression. Vγ9Vδ2 T cells with a TEM (effector memory) phenotype and producing proinflammatory cytokines were correlated with disease activity score (DAS28). The comparison of miRNA expression among Vγ9Vδ2 T-cell subsets from RA patients and HD showed a lower level of miR-106a-5p and miR-20a-5p, and a higher level of miR-21a-5p, among Vγ9Vδ2 TEM cells, and a lower level of miR-19b-3p among Vγ9Vδ2 TCM (central memory) cells was also found. These differentially expressed miRNAs correlated with higher levels of expression of interleukin (IL)-8, IL-6, and PDCD4 genes. Conclusions Our results provide evidence for a role of miR-106a, miR-19-3p, miR-20a, and miR-21a in the regulation of Vγ9Vδ2 T-cell function in RA patients and suggest the possibility that the miRNA17–92 family and Vγ9Vδ2 T cells contribute to the pathogenesis of RA.
- Published
- 2018
46. Deep Immunoprofiling of Large-Scale Tuberculosis Dataset at Single Cell Resolution Reveals a CD81 bright γδ T Cell Population Associated with Latency.
- Author
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Shekarkar Azgomi M, Badami GD, Di Caro M, Tamburini B, Fallo M, Dieli C, Ebrahimi K, Dieli F, La Manna MP, and Caccamo N
- Subjects
- Humans, Tetraspanin 28 metabolism, Single-Cell Analysis, Latent Tuberculosis immunology, Tuberculosis immunology, Tuberculosis microbiology, Female, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, Adult, Male, Receptors, Antigen, T-Cell, gamma-delta metabolism, Mycobacterium tuberculosis immunology
- Abstract
Tuberculosis (TB) remains one of the leading causes of death among infectious diseases, with 10.6 million new cases and 1.3 million deaths reported in 2022, according to the most recent WHO report. Early studies have shown an expansion of γδ T cells following TB infection in both experimental models and humans, indicating their abundance among lung lymphocytes and suggesting a role in protective immune responses against Mycobacterium tuberculosis ( M. tuberculosis ) infection. In this study, we hypothesized that distinct subsets of γδ T cells are associated with either protection against or disease progression in TB. To explore this, we applied large-scale scRNA-seq and bulk RNA-seq data integration to define the phenotypic and molecular characteristics of peripheral blood γδ T cells. Our analysis identified five unique γδ T subclusters, each with distinct functional profiles. Notably, we identified a unique cluster significantly enriched in the TCR signaling pathway, with high CD81 expression as a conserved marker. This distinct molecular signature suggests a specialized role for this cluster in immune signaling and regulation of immune response against M. tuberculosis . Flow cytometry confirmed our in silico results, showing that the mean fluorescence intensity (MFI) values of CD81 expression on γδ T cells were significantly increased in individuals with latent TB infection (TBI) compared to those with active TB (ATB). This finding underscores the importance of CD81 and its associated signaling mechanisms in modulating the activity and function of γδ T cells under TBI conditions, providing insights into potential therapeutic targets for TB management.
- Published
- 2024
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47. Phenotypic and Immunometabolic Aspects on Stem Cell Memory and Resident Memory CD8 + T Cells.
- Author
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La Manna MP, Shekarkar Azgomi M, Tamburini B, Badami GD, Mohammadnezhad L, Dieli F, and Caccamo N
- Subjects
- Memory T Cells, Phenotype, Stem Cells, CD8-Positive T-Lymphocytes, Immunologic Memory
- Abstract
The immune system, smartly and surprisingly, saves the exposure of a particular pathogen in its memory and reacts to the pathogen very rapidly, preventing serious diseases. Immunologists have long been fascinated by understanding the ability to recall and respond faster and more vigorously to a pathogen, known as "memory". T-cell populations can be better described by using more sophisticated techniques to define phenotype, transcriptional and epigenetic signatures and metabolic pathways (single-cell resolution), which uncovered the heterogeneity of the memory T-compartment. Phenotype, effector functions, maintenance, and metabolic pathways help identify these different subsets. Here, we examine recent developments in the characterization of the heterogeneity of the memory T cell compartment. In particular, we focus on the emerging role of CD8
+ TRM and TSCM cells, providing evidence on how their immunometabolism or modulation can play a vital role in their generation and maintenance in chronic conditions such as infections or autoimmune diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 La Manna, Shekarkar Azgomi, Tamburini, Badami, Mohammadnezhad, Dieli and Caccamo.)- Published
- 2022
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48. A Rapid and Simple Multiparameter Assay to Quantify Spike-Specific CD4 and CD8 T Cells after SARS-CoV-2 Vaccination: A Preliminary Report.
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Shekarkar Azgomi M, La Manna MP, Badami GD, Ragonese P, Trizzino A, Dieli F, and Caccamo N
- Abstract
mRNA and Adenovirus vaccines for COVID-19 are used to induce humoral and cell-mediated immunity, with the aim to generate both SARS-CoV-2 B and T memory cells. In present study, we described a simple assay to detect and quantify Spike-specific CD4
+ and CD8+ T cell responses induced by vaccination in healthy donors and in subjects with B cell compart impairment, in which antibody response is absent due to primary immunodeficiencies or CD20 depleting therapy. We detect and quantified memory T cell immune responses against SARS-CoV-2 evocated by vaccination in both groups, irrespective to the humoral response. Furthermore, we identified TNF-α as the main cytokine produced by T memory cells, after antigen-specific stimulation in vitro, that could be considered, other than IFN-γ, an additional biomarker of induction of T memory cells upon vaccination. Further studies on the vaccine-induced T cell responses could be crucial, not only in healthy people but also in immunocompromised subjects, where antigen specific T cells responses play a protective role against SARS-CoV-2.- Published
- 2021
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49. HLA-E-restricted CD8 + T Lymphocytes Efficiently Control Mycobacterium tuberculosis and HIV-1 Coinfection.
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La Manna MP, Orlando V, Prezzemolo T, Di Carlo P, Cascio A, Delogu G, Poli G, Sullivan LC, Brooks AG, Dieli F, and Caccamo N
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- Adult, Antigens, Bacterial immunology, Down-Regulation immunology, Female, Humans, Lymphocyte Activation immunology, Lymphocyte Count methods, Male, Middle Aged, HLA-E Antigens, CD8-Positive T-Lymphocytes immunology, Coinfection immunology, HIV Infections immunology, HIV-1 immunology, HLA-A2 Antigen immunology, Histocompatibility Antigens Class I immunology, Mycobacterium tuberculosis immunology, Tuberculosis immunology
- Abstract
We investigated the contribution of human leukocyte antigen A2 (HLA-A2) and HLA-E-restricted CD8
+ T cells in patients with Mycobacterium tuberculosis and human immunodeficiency virus 1 (HIV-1) coinfection. HIV-1 downregulates HLA-A, -B, and -C molecules in infected cells, thus influencing recognition by HLA class I-restricted CD8+ T cells but not by HLA-E-restricted CD8+ T cells, owing to the inability of the virus to downmodulate their expression. Therefore, antigen-specific HLA-E-restricted CD8+ T cells could play a protective role in Mycobacterium tuberculosis and HIV-1 coinfection. HLA-E- and HLA-A2-restricted Mycobacterium tuberculosis -specific CD8+ T cells were tested in vitro for cytotoxic and microbicidal activities, and their frequencies and phenotypes were evaluated ex vivo in patients with active tuberculosis and concomitant HIV-1 infection. HIV-1 and Mycobacterium tuberculosis coinfection caused downmodulation of HLA-A2 expression in human monocyte-derived macrophages associated with resistance to lysis by HLA-A2-restricted CD8+ T cells and failure to restrict the growth of intracellular Mycobacterium tuberculosis . Conversely, HLA-E surface expression and HLA-E-restricted cytolytic and microbicidal CD8 responses were not affected. HLA-E-restricted and Mycobacterium tuberculosis -specific CD8+ T cells were expanded in the circulation of patients with Mycobacterium tuberculosis /HIV-1 coinfection, as measured by tetramer staining, but displayed a terminally differentiated and exhausted phenotype that was rescued in vitro by anti-PD-1 (programmed cell death protein 1) monoclonal antibody. Together, these results indicate that HLA-E-restricted and Mycobacterium tuberculosis -specific CD8+ T cells in patients with Mycobacterium tuberculosis /HIV-1 coinfection have an exhausted phenotype and fail to expand in vitro in response to antigen stimulation, which can be restored by blocking the PD-1 pathway using the specific monoclonal antibody nivolumab.- Published
- 2020
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50. Analysis of interferon-gamma producing cells during infections by Yersinia enterocolitica O:9 and Brucella abortus in cattle.
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Agnone A, La Manna MP, Vesco G, Gargano V, Macaluso G, Dieli F, Sireci G, and Villari S
- Subjects
- Animals, Cattle, Flow Cytometry veterinary, Leukocytes, Mononuclear immunology, Brucella abortus physiology, Brucellosis, Bovine immunology, Interferon-gamma immunology, Yersinia Infections immunology, Yersinia enterocolitica physiology
- Abstract
One of the major constraints in the diagnosis of animal brucellosis is the cross-reactivity that occurs between Brucella and Yersinia surface antigens. With the aim to find a method to distinguish Brucella from Yersinia infection, the expansion of interferon gamma producing (IFN-γ+) T cell subsets obtained from peripheral blood mononuclear cells (PBMC) isolated from cattle either infected by Brucella abortus or experimentally immunized with Yersinia enterocolitica O:9 were compared. The lymphocytes were analyzed by flow cytometry after PBMC were in vitro re-exposed to Yersinia or Brucella antigens. The results highlighted a statistically significant difference in the expansion of the CD4+ and CD8+ IFN-γ+ T cells occurring when PBMC of animals immunized with Yersinia are in vitro exposed to Y. enterocolitica O:9 antigen but not to Brucella antigen. This method could thus be suggested in those cases where results obtained by serodiagnosis need to be further clarified.
- Published
- 2019
- Full Text
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