17 results on '"Piffaretti, Pietro'
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2. Enhancing bacteriophage therapeutics through in situ production and release of heterologous antimicrobial effectors
- Author
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Du, Jiemin, Meile, Susanne, Baggenstos, Jasmin, Jäggi, Tobias, Piffaretti, Pietro, Hunold, Laura, Matter, Cassandra I., Leitner, Lorenz, Kessler, Thomas M., Loessner, Martin J., Kilcher, Samuel, and Dunne, Matthew
- Published
- 2023
- Full Text
- View/download PDF
3. Autoantibodies against chemokines post-SARS-CoV-2 infection correlate with disease course
- Author
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Muri, Jonathan, Cecchinato, Valentina, Cavalli, Andrea, Shanbhag, Akanksha A., Matkovic, Milos, Biggiogero, Maira, Maida, Pier Andrea, Moritz, Jacques, Toscano, Chiara, Ghovehoud, Elaheh, Furlan, Raffaello, Barbic, Franca, Voza, Antonio, De Nadai, Guendalina, Cervia, Carlo, Zurbuchen, Yves, Taeschler, Patrick, Murray, Lilly A., Danelon-Sargenti, Gabriela, Moro, Simone, Gong, Tao, Piffaretti, Pietro, Bianchini, Filippo, Crivelli, Virginia, Podešvová, Lucie, Pedotti, Mattia, Jarrossay, David, Sgrignani, Jacopo, Thelen, Sylvia, Uhr, Mario, Bernasconi, Enos, Rauch, Andri, Manzo, Antonio, Ciurea, Adrian, Rocchi, Marco B. L., Varani, Luca, Moser, Bernhard, Bottazzi, Barbara, Thelen, Marcus, Fallon, Brian A., Boyman, Onur, Mantovani, Alberto, Garzoni, Christian, Franzetti-Pellanda, Alessandra, Uguccioni, Mariagrazia, and Robbiani, Davide F.
- Published
- 2023
- Full Text
- View/download PDF
4. Enhancing bacteriophage therapeutics through in situ production and release of heterologous antimicrobial effectors
- Author
-
Du, Jiemin; https://orcid.org/0000-0002-1246-6508, Meile, Susanne; https://orcid.org/0000-0001-8786-7157, Baggenstos, Jasmin, Jäggi, Tobias, Piffaretti, Pietro; https://orcid.org/0000-0001-7621-0475, Hunold, Laura, Matter, Cassandra I; https://orcid.org/0000-0002-5450-8614, Leitner, Lorenz; https://orcid.org/0000-0001-5764-3494, Kessler, Thomas M; https://orcid.org/0000-0002-1991-5919, Loessner, Martin J; https://orcid.org/0000-0002-8162-2631, Kilcher, Samuel; https://orcid.org/0000-0002-1162-6549, Dunne, Matthew; https://orcid.org/0000-0002-2329-8183, Du, Jiemin; https://orcid.org/0000-0002-1246-6508, Meile, Susanne; https://orcid.org/0000-0001-8786-7157, Baggenstos, Jasmin, Jäggi, Tobias, Piffaretti, Pietro; https://orcid.org/0000-0001-7621-0475, Hunold, Laura, Matter, Cassandra I; https://orcid.org/0000-0002-5450-8614, Leitner, Lorenz; https://orcid.org/0000-0001-5764-3494, Kessler, Thomas M; https://orcid.org/0000-0002-1991-5919, Loessner, Martin J; https://orcid.org/0000-0002-8162-2631, Kilcher, Samuel; https://orcid.org/0000-0002-1162-6549, and Dunne, Matthew; https://orcid.org/0000-0002-2329-8183
- Abstract
Bacteriophages operate via pathogen-specific mechanisms of action distinct from conventional, broad-spectrum antibiotics and are emerging as promising alternative antimicrobials. However, phage-mediated killing is often limited by bacterial resistance development. Here, we engineer phages for target-specific effector gene delivery and host-dependent production of colicin-like bacteriocins and cell wall hydrolases. Using urinary tract infection (UTI) as a model, we show how heterologous effector phage therapeutics (HEPTs) suppress resistance and improve uropathogen killing by dual phage- and effector-mediated targeting. Moreover, we designed HEPTs to control polymicrobial uropathogen communities through production of effectors with cross-genus activity. Using phage-based companion diagnostics, we identified potential HEPT responder patients and treated their urine ex vivo. Compared to wildtype phage, a colicin E7-producing HEPT demonstrated superior control of patient E. coli bacteriuria. Arming phages with heterologous effectors paves the way for successful UTI treatment and represents a versatile tool to enhance and adapt phage-based precision antimicrobials.
- Published
- 2023
5. Engineered reporter phages for detection of Escherichia coli, Enterococcus, and Klebsiella in urine
- Author
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Meile, Susanne; https://orcid.org/0000-0001-8786-7157, Du, Jiemin; https://orcid.org/0000-0002-1246-6508, Staubli, Samuel; https://orcid.org/0009-0009-0984-1889, Grossmann, Sebastian; https://orcid.org/0000-0002-4141-079X, Koliwer-Brandl, Hendrik; https://orcid.org/0000-0003-1613-5615, Piffaretti, Pietro; https://orcid.org/0000-0001-7621-0475, Leitner, Lorenz; https://orcid.org/0000-0001-5764-3494, Matter, Cassandra I; https://orcid.org/0000-0002-5450-8614, Baggenstos, Jasmin, Hunold, Laura, Milek, Sonja, Guebeli, Christian; https://orcid.org/0000-0002-1706-0187, Kozomara-Hocke, Marko, Neumeier, Vera; https://orcid.org/0000-0002-8149-3710, Botteon, Angela, Klumpp, Jochen; https://orcid.org/0000-0003-3410-2702, Marschall, Jonas; https://orcid.org/0000-0002-0052-3210, McCallin, Shawna; https://orcid.org/0000-0002-4277-7753, Zbinden, Reinhard, Kessler, Thomas M; https://orcid.org/0000-0002-1991-5919, Loessner, Martin J; https://orcid.org/0000-0002-8162-2631, Dunne, Matthew; https://orcid.org/0000-0002-2329-8183, Kilcher, Samuel; https://orcid.org/0000-0002-1162-6549, Meile, Susanne; https://orcid.org/0000-0001-8786-7157, Du, Jiemin; https://orcid.org/0000-0002-1246-6508, Staubli, Samuel; https://orcid.org/0009-0009-0984-1889, Grossmann, Sebastian; https://orcid.org/0000-0002-4141-079X, Koliwer-Brandl, Hendrik; https://orcid.org/0000-0003-1613-5615, Piffaretti, Pietro; https://orcid.org/0000-0001-7621-0475, Leitner, Lorenz; https://orcid.org/0000-0001-5764-3494, Matter, Cassandra I; https://orcid.org/0000-0002-5450-8614, Baggenstos, Jasmin, Hunold, Laura, Milek, Sonja, Guebeli, Christian; https://orcid.org/0000-0002-1706-0187, Kozomara-Hocke, Marko, Neumeier, Vera; https://orcid.org/0000-0002-8149-3710, Botteon, Angela, Klumpp, Jochen; https://orcid.org/0000-0003-3410-2702, Marschall, Jonas; https://orcid.org/0000-0002-0052-3210, McCallin, Shawna; https://orcid.org/0000-0002-4277-7753, Zbinden, Reinhard, Kessler, Thomas M; https://orcid.org/0000-0002-1991-5919, Loessner, Martin J; https://orcid.org/0000-0002-8162-2631, Dunne, Matthew; https://orcid.org/0000-0002-2329-8183, and Kilcher, Samuel; https://orcid.org/0000-0002-1162-6549
- Abstract
The rapid detection and species-level differentiation of bacterial pathogens facilitates antibiotic stewardship and improves disease management. Here, we develop a rapid bacteriophage-based diagnostic assay to detect the most prevalent pathogens causing urinary tract infections: Escherichia coli, Enterococcus spp., and Klebsiella spp. For each uropathogen, two virulent phages were genetically engineered to express a nanoluciferase reporter gene upon host infection. Using 206 patient urine samples, reporter phage-induced bioluminescence was quantified to identify bacteriuria and the assay was benchmarked against conventional urinalysis. Overall, E. coli, Enterococcus spp., and Klebsiella spp. were each detected with high sensitivity (68%, 78%, 87%), specificity (99%, 99%, 99%), and accuracy (90%, 94%, 98%) at a resolution of ≥10$^{3}$ CFU/ml within 5 h. We further demonstrate how bioluminescence in urine can be used to predict phage antibacterial activity, demonstrating the future potential of reporter phages as companion diagnostics that guide patient-phage matching prior to therapeutic phage application.
- Published
- 2023
6. Autoantibodies against chemokines post-SARS-CoV-2 infection correlate with disease course
- Author
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Muri, Jonathan; https://orcid.org/0000-0002-6476-3766, Cecchinato, Valentina; https://orcid.org/0000-0001-7415-8706, Cavalli, Andrea; https://orcid.org/0000-0003-4063-4502, Shanbhag, Akanksha A; https://orcid.org/0000-0002-1676-2478, Matkovic, Milos; https://orcid.org/0000-0002-4872-1996, Biggiogero, Maira, Maida, Pier Andrea, Moritz, Jacques, Toscano, Chiara; https://orcid.org/0000-0002-0309-946X, Ghovehoud, Elaheh; https://orcid.org/0000-0002-0366-2670, Furlan, Raffaello, Barbic, Franca; https://orcid.org/0000-0002-8283-1988, Voza, Antonio, De Nadai, Guendalina, Cervia, Carlo; https://orcid.org/0000-0001-7120-8739, Zurbuchen, Yves; https://orcid.org/0000-0001-5387-9950, Taeschler, Patrick; https://orcid.org/0000-0003-0522-7629, Murray, Lilly A; https://orcid.org/0000-0001-6153-5277, Danelon-Sargenti, Gabriela, Moro, Simone, Gong, Tao; https://orcid.org/0000-0002-9414-6902, Piffaretti, Pietro; https://orcid.org/0000-0001-7621-0475, Bianchini, Filippo; https://orcid.org/0000-0002-0746-7629, Crivelli, Virginia; https://orcid.org/0000-0003-2494-7242, Podešvová, Lucie; https://orcid.org/0000-0003-1054-2252, Pedotti, Mattia; https://orcid.org/0000-0003-1370-9505, Jarrossay, David; https://orcid.org/0000-0002-0924-6395, Sgrignani, Jacopo; https://orcid.org/0000-0002-8633-1032, Thelen, Sylvia, Uhr, Mario, et al, Ciurea, Adrian; https://orcid.org/0000-0002-7870-7132, Boyman, Onur; https://orcid.org/0000-0001-8279-5545, Muri, Jonathan; https://orcid.org/0000-0002-6476-3766, Cecchinato, Valentina; https://orcid.org/0000-0001-7415-8706, Cavalli, Andrea; https://orcid.org/0000-0003-4063-4502, Shanbhag, Akanksha A; https://orcid.org/0000-0002-1676-2478, Matkovic, Milos; https://orcid.org/0000-0002-4872-1996, Biggiogero, Maira, Maida, Pier Andrea, Moritz, Jacques, Toscano, Chiara; https://orcid.org/0000-0002-0309-946X, Ghovehoud, Elaheh; https://orcid.org/0000-0002-0366-2670, Furlan, Raffaello, Barbic, Franca; https://orcid.org/0000-0002-8283-1988, Voza, Antonio, De Nadai, Guendalina, Cervia, Carlo; https://orcid.org/0000-0001-7120-8739, Zurbuchen, Yves; https://orcid.org/0000-0001-5387-9950, Taeschler, Patrick; https://orcid.org/0000-0003-0522-7629, Murray, Lilly A; https://orcid.org/0000-0001-6153-5277, Danelon-Sargenti, Gabriela, Moro, Simone, Gong, Tao; https://orcid.org/0000-0002-9414-6902, Piffaretti, Pietro; https://orcid.org/0000-0001-7621-0475, Bianchini, Filippo; https://orcid.org/0000-0002-0746-7629, Crivelli, Virginia; https://orcid.org/0000-0003-2494-7242, Podešvová, Lucie; https://orcid.org/0000-0003-1054-2252, Pedotti, Mattia; https://orcid.org/0000-0003-1370-9505, Jarrossay, David; https://orcid.org/0000-0002-0924-6395, Sgrignani, Jacopo; https://orcid.org/0000-0002-8633-1032, Thelen, Sylvia, Uhr, Mario, et al, Ciurea, Adrian; https://orcid.org/0000-0002-7870-7132, and Boyman, Onur; https://orcid.org/0000-0001-8279-5545
- Abstract
Infection with severe acute respiratory syndrome coronavirus 2 associates with diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse coronavirus disease 2019 (COVID-19) outcomes. Here we discovered that antibodies against specific chemokines were omnipresent post-COVID-19, were associated with favorable disease outcome and negatively correlated with the development of long COVID at 1 yr post-infection. Chemokine antibodies were also present in HIV-1 infection and autoimmune disorders, but they targeted different chemokines compared with COVID-19. Monoclonal antibodies derived from COVID-19 convalescents that bound to the chemokine N-loop impaired cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising chemokine antibodies may modulate the inflammatory response and thus bear therapeutic potential.
- Published
- 2023
7. Autoantibodies against chemokines post-SARS-CoV-2 infection correlate with disease course
- Author
-
Jonathan Muri, Valentina Cecchinato, Andrea Cavalli, Akanksha A. Shanbhag, Milos Matkovic, Maira Biggiogero, Pier Andrea Maida, Jacques Moritz, Chiara Toscano, Elaheh Ghovehoud, Raffaello Furlan, Franca Barbic, Antonio Voza, Guendalina De Nadai, Carlo Cervia, Yves Zurbuchen, Patrick Taeschler, Lilly A. Murray, Gabriela Danelon-Sargenti, Simone Moro, Tao Gong, Pietro Piffaretti, Filippo Bianchini, Virginia Crivelli, Lucie Podešvová, Mattia Pedotti, David Jarrossay, Jacopo Sgrignani, Sylvia Thelen, Mario Uhr, Enos Bernasconi, Andri Rauch, Antonio Manzo, Adrian Ciurea, Marco B. L. Rocchi, Luca Varani, Bernhard Moser, Barbara Bottazzi, Marcus Thelen, Brian A. Fallon, Onur Boyman, Alberto Mantovani, Christian Garzoni, Alessandra Franzetti-Pellanda, Mariagrazia Uguccioni, and Davide F. Robbiani
- Subjects
Immunology ,Immunology and Allergy ,610 Medicine & health ,610 Medizin und Gesundheit - Abstract
Infection with severe acute respiratory syndrome coronavirus 2 associates with diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse coronavirus disease 2019 (COVID-19) outcomes. Here we discovered that antibodies against specific chemokines were omnipresent post-COVID-19, were associated with favorable disease outcome and negatively correlated with the development of long COVID at 1 yr post-infection. Chemokine antibodies were also present in HIV-1 infection and autoimmune disorders, but they targeted different chemokines compared with COVID-19. Monoclonal antibodies derived from COVID-19 convalescents that bound to the chemokine N-loop impaired cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising chemokine antibodies may modulate the inflammatory response and thus bear therapeutic potential.
- Published
- 2023
- Full Text
- View/download PDF
8. Engineered reporter phages for rapid detection ofEscherichia coli, Klebsiellaspp., andEnterococcusspp. in urine
- Author
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Susanne Meile, Jiemin Du, Samuel Staubli, Sebastian Grossman, Hendrik Koliwer-Brandl, Pietro Piffaretti, Lorenz Leitner, Cassandra I. Matter, Jasmin Baggenstos, Laura Hunold, Sonja Milek, Christian Gübeli, Marko Kozomara-Hocke, Vera Neumeier, Angela Botteon, Jochen Klumpp, Jonas Marschall, Shawna McCallin, Reinhard Zbinden, Thomas M. Kessler, Martin J. Loessner, Matthew Dunne, and Samuel Kilcher
- Abstract
The rapid detection and species-level differentiation of bacterial pathogens facilitates antibiotic stewardship and improves disease management. Here, we develop a rapid bacteriophage-based diagnostic assay to detect the most prevalent pathogens causing urinary tract infections:Escherichia coli, Klebsiellaspp., andEnterococcusspp. For each uropathogen, two virulent phages were genetically engineered to express a nanoluciferase reporter gene upon host infection. Using 206 patient urine samples, reporter phage-induced bioluminescence was quantified to identify bacteriuria and the assay was benchmarked against conventional urinalysis. Overall,E. coli, Klebsiellaspp., andEnterococcusspp. were each detected with high sensitivity (68%, 78%, 85%), specificity (99%, 99%, 99%), and accuracy (90%, 94%, 96%) at a resolution of ⩾103CFU/ml within 5 h. We further demonstrate how bioluminescence in urine can be used to predict phage antibacterial activity, demonstrating the future potential of reporter phages as companion diagnostics that guide patient-phage matching prior to therapeutic phage application.
- Published
- 2022
- Full Text
- View/download PDF
9. Engineered reporter phages for rapid detection ofEscherichia coli, Klebsiellaspp., andEnterococcusspp. in urine
- Author
-
Meile, Susanne, primary, Du, Jiemin, additional, Staubli, Samuel, additional, Grossman, Sebastian, additional, Koliwer-Brandl, Hendrik, additional, Piffaretti, Pietro, additional, Leitner, Lorenz, additional, Matter, Cassandra I., additional, Baggenstos, Jasmin, additional, Hunold, Laura, additional, Milek, Sonja, additional, Gübeli, Christian, additional, Kozomara-Hocke, Marko, additional, Neumeier, Vera, additional, Botteon, Angela, additional, Klumpp, Jochen, additional, Marschall, Jonas, additional, McCallin, Shawna, additional, Zbinden, Reinhard, additional, Kessler, Thomas M., additional, Loessner, Martin J., additional, Dunne, Matthew, additional, and Kilcher, Samuel, additional
- Published
- 2022
- Full Text
- View/download PDF
10. Anti-chemokine antibodies after SARS-CoV-2 infection correlate with favorable disease course
- Author
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Jonathan Muri, Valentina Cecchinato, Andrea Cavalli, Akanksha A. Shanbhag, Milos Matkovic, Maira Biggiogero, Pier Andrea Maida, Jacques Moritz, Chiara Toscano, Elaheh Ghovehoud, Raffaello Furlan, Franca Barbic, Antonio Voza, Guendalina De Nadai, Carlo Cervia, Yves Zurbuchen, Patrick Taeschler, Lilly A. Murray, Gabriela Danelon-Sargenti, Simone Moro, Tao Gong, Pietro Piffaretti, Filippo Bianchini, Virginia Crivelli, Lucie Podešvová, Mattia Pedotti, David Jarrossay, Jacopo Sgrignani, Sylvia Thelen, Mario Uhr, Enos Bernasconi, Andri Rauch, Antonio Manzo, Adrian Ciurea, Marco B.L. Rocchi, Luca Varani, Bernhard Moser, Barbara Bottazzi, Marcus Thelen, Brian A. Fallon, Onur Boyman, Alberto Mantovani, Christian Garzoni, Alessandra Franzetti-Pellanda, Mariagrazia Uguccioni, and Davide F. Robbiani
- Subjects
Article - Abstract
Infection by SARS-CoV-2 leads to diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse COVID-19 outcomes. Instead, we discovered that antibodies against specific chemokines are omnipresent after COVID-19, associated with favorable disease, and predictive of lack of long COVID symptoms at one year post infection. Anti-chemokine antibodies are present also in HIV-1 infection and autoimmune disorders, but they target different chemokines than those in COVID-19. Monoclonal antibodies derived from COVID- 19 convalescents that bind to the chemokine N-loop impair cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising anti-chemokine antibodies associated with favorable COVID-19 may be beneficial by modulating the inflammatory response and thus bear therapeutic potential.One-Sentence Summary:Naturally arising anti-chemokine antibodies associate with favorable COVID-19 and predict lack of long COVID.
- Published
- 2022
11. Enhancing bacteriophage therapeutics throughin situproduction and release of heterologous antimicrobial effectors
- Author
-
Jiemin Du, Susanne Meile, Jasmin Baggenstos, Tobias Jäggi, Pietro Piffaretti, Laura Hunold, Cassandra I. Matter, Lorenz Leitner, Thomas M. Kessler, Martin J. Loessner, Samuel Kilcher, and Matthew Dunne
- Abstract
Bacteriophages operate via pathogen-specific mechanisms of action distinct from conventional, broad-spectrum antibiotics and are emerging as promising alternatives. However, phage-mediated killing is often limited by bacterial resistance development (1,2). Here, we engineer phages for target-specific effector gene delivery and host-dependent production of colicin-like bacteriocins and cell wall hydrolases. Using urinary tract infection (UTI) as a model, we show how heterologous effector phage therapeutics (HEPTs) suppress resistance and improve uropathogen killing by dual phage- and effector-mediated targeting. Moreover, we designed HEPTs to control polymicrobial uropathogen communities through production of effectors with cross-genus activity. Using a phage-based companion diagnostic (3), we identified potential HEPT responder patients and treated their urineex vivo. Compared to wildtype phage, a colicin E7-producing HEPT demonstrated superior control of patientE. colibacteriuria. Arming phages with heterologous effectors paves the way for successful UTI treatment and represents a versatile tool to enhance and adapt phage-based precision antimicrobials.
- Published
- 2022
- Full Text
- View/download PDF
12. Anti-chemokine antibodies after SARS-CoV-2 infection correlate with favorable disease course
- Author
-
Muri, Jonathan; https://orcid.org/0000-0002-6476-3766, Cecchinato, Valentina; https://orcid.org/0000-0001-7415-8706, Cavalli, Andrea; https://orcid.org/0000-0003-4063-4502, Shanbhag, Akanksha A; https://orcid.org/0000-0002-1676-2478, Matkovic, Milos; https://orcid.org/0000-0002-4872-1996, Biggiogero, Maira, Maida, Pier Andrea, Toscano, Chiara; https://orcid.org/0000-0002-0309-946X, Ghovehoud, Elaheh; https://orcid.org/0000-0002-0366-2670, Danelon-Sargenti, Gabriela, Gong, Tao; https://orcid.org/0000-0002-9414-6902, Piffaretti, Pietro; https://orcid.org/0000-0001-7621-0475, Bianchini, Filippo; https://orcid.org/0000-0002-0746-7629, Crivelli, Virginia; https://orcid.org/0000-0003-2494-7242, Podešvová, Lucie; https://orcid.org/0000-0003-1054-2252, Pedotti, Mattia; https://orcid.org/0000-0003-1370-9505, Jarrossay, David; https://orcid.org/0000-0002-0924-6395, Sgrignani, Jacopo; https://orcid.org/0000-0002-8633-1032, Thelen, Sylvia, Uhr, Mario, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Rauch, Andri; https://orcid.org/0000-0001-5297-6062, Manzo, Antonio; https://orcid.org/0000-0002-9743-6008, Ciurea, Adrian; https://orcid.org/0000-0002-7870-7132, Rocchi, Marco B L; https://orcid.org/0000-0002-0056-5795, Varani, Luca; https://orcid.org/0000-0002-0963-0987, Moser, Bernhard, Thelen, Marcus; https://orcid.org/0000-0002-3443-1605, Garzoni, Christian, Franzetti-Pellanda, Alessandra, Uguccioni, Mariagrazia, Robbiani, Davide F, Muri, Jonathan; https://orcid.org/0000-0002-6476-3766, Cecchinato, Valentina; https://orcid.org/0000-0001-7415-8706, Cavalli, Andrea; https://orcid.org/0000-0003-4063-4502, Shanbhag, Akanksha A; https://orcid.org/0000-0002-1676-2478, Matkovic, Milos; https://orcid.org/0000-0002-4872-1996, Biggiogero, Maira, Maida, Pier Andrea, Toscano, Chiara; https://orcid.org/0000-0002-0309-946X, Ghovehoud, Elaheh; https://orcid.org/0000-0002-0366-2670, Danelon-Sargenti, Gabriela, Gong, Tao; https://orcid.org/0000-0002-9414-6902, Piffaretti, Pietro; https://orcid.org/0000-0001-7621-0475, Bianchini, Filippo; https://orcid.org/0000-0002-0746-7629, Crivelli, Virginia; https://orcid.org/0000-0003-2494-7242, Podešvová, Lucie; https://orcid.org/0000-0003-1054-2252, Pedotti, Mattia; https://orcid.org/0000-0003-1370-9505, Jarrossay, David; https://orcid.org/0000-0002-0924-6395, Sgrignani, Jacopo; https://orcid.org/0000-0002-8633-1032, Thelen, Sylvia, Uhr, Mario, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Rauch, Andri; https://orcid.org/0000-0001-5297-6062, Manzo, Antonio; https://orcid.org/0000-0002-9743-6008, Ciurea, Adrian; https://orcid.org/0000-0002-7870-7132, Rocchi, Marco B L; https://orcid.org/0000-0002-0056-5795, Varani, Luca; https://orcid.org/0000-0002-0963-0987, Moser, Bernhard, Thelen, Marcus; https://orcid.org/0000-0002-3443-1605, Garzoni, Christian, Franzetti-Pellanda, Alessandra, Uguccioni, Mariagrazia, and Robbiani, Davide F
- Abstract
Infection by SARS-CoV-2 leads to diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse COVID-19 outcomes. Instead, we discovered that antibodies against specific chemokines are omnipresent after COVID-19, associated with favorable disease, and predictive of lack of long COVID symptoms at one year post infection. Anti-chemokine antibodies are present also in HIV-1 and autoimmune disorders, but they target different chemokines than those in COVID-19. Finally, monoclonal antibodies derived from COVID- 19 convalescents that bind to the chemokine N-loop impair cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising anti-chemokine antibodies associated with favorable COVID-19 may be beneficial by modulating the inflammatory response and thus bear therapeutic potential. One-sentence summary: Naturally arising anti-chemokine antibodies associate with favorable COVID-19 and are predictive of lack of long COVID.
- Published
- 2022
13. Anti-chemokine antibodies after SARS-CoV-2 infection correlate with favorable disease course
- Author
-
Muri, Jonathan, primary, Cecchinato, Valentina, additional, Cavalli, Andrea, additional, Shanbhag, Akanksha A., additional, Matkovic, Milos, additional, Biggiogero, Maira, additional, Maida, Pier Andrea, additional, Moritz, Jacques, additional, Toscano, Chiara, additional, Ghovehoud, Elaheh, additional, Furlan, Raffaello, additional, Barbic, Franca, additional, Voza, Antonio, additional, Nadai, Guendalina De, additional, Cervia, Carlo, additional, Zurbuchen, Yves, additional, Taeschler, Patrick, additional, Murray, Lilly A., additional, Danelon-Sargenti, Gabriela, additional, Moro, Simone, additional, Gong, Tao, additional, Piffaretti, Pietro, additional, Bianchini, Filippo, additional, Crivelli, Virginia, additional, Podešvová, Lucie, additional, Pedotti, Mattia, additional, Jarrossay, David, additional, Sgrignani, Jacopo, additional, Thelen, Sylvia, additional, Uhr, Mario, additional, Bernasconi, Enos, additional, Rauch, Andri, additional, Manzo, Antonio, additional, Ciurea, Adrian, additional, Rocchi, Marco B.L., additional, Varani, Luca, additional, Moser, Bernhard, additional, Bottazzi, Barbara, additional, Thelen, Marcus, additional, Fallon, Brian A., additional, Boyman, Onur, additional, Mantovani, Alberto, additional, Garzoni, Christian, additional, Franzetti-Pellanda, Alessandra, additional, Uguccioni, Mariagrazia, additional, and Robbiani, Davide F., additional
- Published
- 2022
- Full Text
- View/download PDF
14. Enhancing bacteriophage therapeutics throughin situproduction and release of heterologous antimicrobial effectors
- Author
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Du, Jiemin, primary, Meile, Susanne, additional, Baggenstos, Jasmin, additional, Jäggi, Tobias, additional, Piffaretti, Pietro, additional, Hunold, Laura, additional, Matter, Cassandra I., additional, Leitner, Lorenz, additional, Kessler, Thomas M., additional, Loessner, Martin J., additional, Kilcher, Samuel, additional, and Dunne, Matthew, additional
- Published
- 2022
- Full Text
- View/download PDF
15. Anti-chemokine antibodies after SARS-CoV-2 infection correlate with favorable disease course
- Author
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Muri, Jonathan, Cecchinato, Valentina, Cavalli, Andrea, Shanbhag, Akanksha A, Matkovic, Milos, Biggiogero, Maira, Maida, Pier Andrea, Toscano, Chiara, Ghovehoud, Elaheh, Danelon-Sargenti, Gabriela, Gong, Tao, Piffaretti, Pietro, Bianchini, Filippo, Crivelli, Virginia, Podešvová, Lucie, Pedotti, Mattia, Jarrossay, David, Sgrignani, Jacopo, Thelen, Sylvia, Uhr, Mario, Bernasconi, Enos, Rauch, Andri, Manzo, Antonio, Ciurea, Adrian, Rocchi, Marco B L, Varani, Luca, Moser, Bernhard, Thelen, Marcus, Garzoni, Christian, Franzetti-Pellanda, Alessandra, Uguccioni, Mariagrazia, Robbiani, Davide F, and University of Zurich
- Subjects
10051 Rheumatology Clinic and Institute of Physical Medicine ,610 Medicine & health - Abstract
Infection by SARS-CoV-2 leads to diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse COVID-19 outcomes. Instead, we discovered that antibodies against specific chemokines are omnipresent after COVID-19, associated with favorable disease, and predictive of lack of long COVID symptoms at one year post infection. Anti-chemokine antibodies are present also in HIV-1 and autoimmune disorders, but they target different chemokines than those in COVID-19. Finally, monoclonal antibodies derived from COVID- 19 convalescents that bind to the chemokine N-loop impair cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising anti-chemokine antibodies associated with favorable COVID-19 may be beneficial by modulating the inflammatory response and thus bear therapeutic potential. One-Sentence Summary Naturally arising anti-chemokine antibodies associate with favorable COVID-19 and are predictive of lack of long COVID.
- Published
- 2022
- Full Text
- View/download PDF
16. Salmonella multimutants enable efficient identification of SPI-2 effector protein function in gut inflammation and systemic colonization.
- Author
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Newson JPM, Gürtler F, Piffaretti P, Meyer A, Sintsova A, Barthel M, Steiger Y, McHugh SC, Enz U, Alto NM, Sunagawa S, and Hardt WD
- Abstract
Salmonella enterica spp. rely on translocation of effector proteins through the SPI-2 encoded type III secretion system (T3SS) to achieve pathogenesis. More than 30 effectors contribute to manipulation of host cells through diverse mechanisms, but interdependency or redundancy between effectors complicates the discovery of effector phenotypes using single mutant strains. Here, we engineer six mutant strains to be deficient in cohorts of SPI-2 effector proteins, as defined by their reported function. Using various animal models of infection, we show that three principle phenotypes define the functional contribution of the SPI-2 T3SS to infection. Multimutant strains deficient for intracellular replication, for manipulation of host cell defences, or for expression of virulence plasmid effectors all showed strong attenuation in vivo , while mutants representing approximately half of the known effector complement showed phenotypes similar to the wild-type parent strain. By additionally removing the SPI-1 T3SS, we find cohorts of effector proteins that contribute to SPI-2 T3SS-driven enhancement of gut inflammation. Further, we provide an example of how iterative mutation can be used to find a minimal number of effector deletions required for attenuation, and thus establish that the SPI-2 effectors SopD2 and GtgE are critical for the promotion of gut inflammation and mucosal pathology. This strategy provides a powerful toolset for simultaneous parallel screening of all known SPI-2 effectors in a single experimental context, and further facilitates the identification of the responsible effectors, and thereby provides an efficient approach to study how individual effectors contribute to disease.
- Published
- 2024
- Full Text
- View/download PDF
17. Anti-chemokine antibodies after SARS-CoV-2 infection correlate with favorable disease course.
- Author
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Muri J, Cecchinato V, Cavalli A, Shanbhag AA, Matkovic M, Biggiogero M, Maida PA, Moritz J, Toscano C, Ghovehoud E, Furlan R, Barbic F, Voza A, Nadai G, Cervia C, Zurbuchen Y, Taeschler P, Murray LA, Danelon-Sargenti G, Moro S, Gong T, Piffaretti P, Bianchini F, Crivelli V, Podešvová L, Pedotti M, Jarrossay D, Sgrignani J, Thelen S, Uhr M, Bernasconi E, Rauch A, Manzo A, Ciurea A, Rocchi MBL, Varani L, Moser B, Bottazzi B, Thelen M, Fallon BA, Boyman O, Mantovani A, Garzoni C, Franzetti-Pellanda A, Uguccioni M, and Robbiani DF
- Abstract
Infection by SARS-CoV-2 leads to diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse COVID-19 outcomes. Instead, we discovered that antibodies against specific chemokines are omnipresent after COVID-19, associated with favorable disease, and predictive of lack of long COVID symptoms at one year post infection. Anti-chemokine antibodies are present also in HIV-1 infection and autoimmune disorders, but they target different chemokines than those in COVID-19. Monoclonal antibodies derived from COVID- 19 convalescents that bind to the chemokine N-loop impair cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising anti-chemokine antibodies associated with favorable COVID-19 may be beneficial by modulating the inflammatory response and thus bear therapeutic potential., One-Sentence Summary: Naturally arising anti-chemokine antibodies associate with favorable COVID-19 and predict lack of long COVID.
- Published
- 2022
- Full Text
- View/download PDF
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