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1. Ceramide present in cholangiocarcinoma-derived extracellular vesicle induces a pro-inflammatory state in monocytes

Author

Oliviero, Barbara, Dei Cas, Michele, Zulueta, Aida, Maiello, Roberta, Villa, Alessandro, Martinelli, Carla, Del Favero, Elena, Falleni, Monica, Montavoci, Linda, Varchetta, Stefania, Mele, Dalila, Donadon, Matteo, Soldani, Cristiana, Franceschini, Barbara, Maestri, Marcello, Piccolo, Gaetano, Barabino, Matteo, Bianchi, Paolo Pietro, Banales, Jesus M., Mantovani, Stefania, Mondelli, Mario U., and Caretti, Anna

Published
2023
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2. Long‐term dynamics of natural killer cells in response to SARS‐CoV‐2 vaccination: Persistently enhanced activity postvaccination

Author

Mele, Dalila, primary, Ottolini, Sabrina, additional, Lombardi, Andrea, additional, Conteianni, Daniela, additional, Bandera, Alessandra, additional, Oliviero, Barbara, additional, Mantovani, Stefania, additional, Cassaniti, Irene, additional, Baldanti, Fausto, additional, Gori, Andrea, additional, Mondelli, Mario U., additional, and Varchetta, Stefania, additional

Published
2024
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3. Unique immunological profile in patients with COVID-19

Author

Varchetta, Stefania, Mele, Dalila, Oliviero, Barbara, Mantovani, Stefania, Ludovisi, Serena, Cerino, Antonella, Bruno, Raffaele, Castelli, Alberto, Mosconi, Mario, Vecchia, Marco, Roda, Silvia, Sachs, Michele, Klersy, Catherine, and Mondelli, Mario U.

Published
2021
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6. Humoral and Cellular Immune Response Elicited by the BNT162b2 COVID-19 Vaccine Booster in Elderly

Author

Dalla Gasperina, Daniela, primary, Veronesi, Giovanni, additional, Castelletti, Carlo M., additional, Varchetta, Stefania, additional, Ottolini, Sabrina, additional, Mele, Dalila, additional, Ferrari, Giuseppe, additional, Shaik, Amruth K. B., additional, Celesti, Fabrizio, additional, Dentali, Francesco, additional, Accolla, Roberto S., additional, and Forlani, Greta, additional

Published
2023
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9. Hepatitis C Virus and the Host: A Mutual Endurance Leaving Indelible Scars in the Host's Immunity.

Author

Mondelli, Mario U., Ottolini, Sabrina, Oliviero, Barbara, Mantovani, Stefania, Cerino, Antonella, Mele, Dalila, and Varchetta, Stefania

Subjects
HEPATITIS C virus, T-cell exhaustion, IMMUNITY, VACCINE effectiveness, IMMUNE response
Abstract

Hepatitis C virus (HCV) has spread worldwide, and it is responsible for potentially severe chronic liver disease and primary liver cancer. Chronic infection remains for life if not spontaneously eliminated and viral persistence profoundly impairs the efficiency of the host's immunity. Attempts have been made to develop an effective vaccine, but efficacy trials have met with failure. The availability of highly efficacious direct-acting antivirals (DAA) has created hope for the progressive elimination of chronic HCV infections; however, this approach requires a monumental global effort. HCV elicits a prompt innate immune response in the host, characterized by a robust production of interferon-α (IFN-α), although interference in IFN-α signaling by HCV proteins may curb this effect. The late appearance of largely ineffective neutralizing antibodies and the progressive exhaustion of T cells, particularly CD8 T cells, result in the inability to eradicate the virus in most infected patients. Moreover, an HCV cure resulting from DAA treatment does not completely restore the normal immunologic homeostasis. Here, we discuss the main immunological features of immune responses to HCV and the epigenetic scars that chronic viral persistence leaves behind. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Ceramide present in cholangiocarcinoma-derived extracellular vesicle induces a pro-inflammatory state in monocytes.

Author

Oliviero, Barbara, primary, Cas, Michele Dei, additional, Zulueta, Aida, additional, Maiello, Roberta, additional, Villa, Alessandro, additional, Martinelli, Carla, additional, Favero, Elena Del, additional, Falleni, Monica, additional, Montavoci, Linda, additional, Varchetta, Stefania, additional, Mele, Dalila, additional, Donadon, Matteo, additional, Soldani, Cristiana, additional, Franceschini, Barbara, additional, Maestri, Marcello, additional, Piccolo, Gaetano, additional, Barabino, Matteo, additional, Bianchi, Paolo, additional, Banales, Jesus M, additional, Mantovani, Stefania, additional, Mondelli, Mario, additional, and Caretti, Anna, additional

Published
2023
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12. Defective DNAM-1 Dependent Cytotoxicity in Hepatocellular Carcinoma-Infiltrating NK Cells

Author

Mantovani, Stefania, primary, Varchetta, Stefania, additional, Mele, Dalila, additional, Maiello, Roberta, additional, Donadon, Matteo, additional, Soldani, Cristiana, additional, Franceschini, Barbara, additional, Torzilli, Guido, additional, Tartaglia, Giuseppe, additional, Maestri, Marcello, additional, Piccolo, Gaetano, additional, Barabino, Matteo, additional, Opocher, Enrico, additional, Bernuzzi, Stefano, additional, Mondelli, Mario U., additional, and Oliviero, Barbara, additional

Published
2022
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13. Early and Polyantigenic CD4 T Cell Responses Correlate with Mild Disease in Acute COVID-19 Donors

Author

Tarke, Alison, primary, Potesta, Marina, additional, Varchetta, Stefania, additional, Fenoglio, Daniela, additional, Iannetta, Marco, additional, Sarmati, Loredana, additional, Mele, Dalila, additional, Dentone, Chiara, additional, Bassetti, Matteo, additional, Montesano, Carla, additional, Mondelli, Mario U., additional, Filaci, Gilberto, additional, Grifoni, Alba, additional, and Sette, Alessandro, additional

Published
2022
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16. MICA/B-targeted antibody promotes NK cell–driven tumor immunity in patients with intrahepatic cholangiocarcinoma

Author

Oliviero, Barbara, primary, Varchetta, Stefania, additional, Mele, Dalila, additional, Pessino, Greta, additional, Maiello, Roberta, additional, Falleni, Monica, additional, Tosi, Delfina, additional, Donadon, Matteo, additional, Soldani, Cristiana, additional, Franceschini, Barbara, additional, Torzilli, Guido, additional, Piccolo, Gaetano, additional, Barabino, Matteo, additional, Opocher, Enrico, additional, Maestri, Marcello, additional, Bernuzzi, Stefano, additional, Wucherpfennig, Kai W., additional, Mondelli, Mario U., additional, and Mantovani, Stefania, additional

Published
2022
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17. High Frequencies of Functional Virus-Specific CD4+ T Cells in SARS-CoV-2 Subjects With Olfactory and Taste Disorders

Author

Mele, Dalila, primary, Calastri, Anna, additional, Maiorano, Eugenia, additional, Cerino, Antonella, additional, Sachs, Michele, additional, Oliviero, Barbara, additional, Mantovani, Stefania, additional, Baldanti, Fausto, additional, Bruno, Raffaele, additional, Benazzo, Marco, additional, Grifoni, Alba, additional, Sette, Alessandro, additional, Mondelli, Mario U., additional, and Varchetta, Stefania, additional

Published
2021
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19. A new algorithm shows superior ability to discriminate liver fibrosis stages in chronic hepatitis C

Author

Varchetta, Stefania, primary, Mele, Dalila, additional, D'Ambrosio, Roberta, additional, Perbellini, Riccardo, additional, Lombardi, Andrea, additional, Rojas, Angela, additional, Paolucci, Stefania, additional, Baldanti, Fausto, additional, Oliviero, Barbara, additional, Mantovani, Stefania, additional, Tinelli, Carmine, additional, De Silvestri, Annalisa, additional, Romero Gomez, Manuel, additional, Lampertico, Pietro, additional, and Mondelli, Mario U., additional

Published
2021
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20. SARS Cov-2 infection in a renal-transplanted patient: A case report

Author

Seminari, Elena, Colaneri, Marta, Sambo, Margherita, Gallazzi, Ilaria, Di Matteo, Angela, Roda, Silvia, Bruno, Raffaele, Mondelli, Mario U., Brunetti, Enrico, Maiocchi, Laura, Zuccaro, Valentina, Pagnucco, Layla, Mariani, Bianca, Ludovisi, Serena, Lissandrin, Raffaella, Parisi, Aldo, Sacchi, Paolo, Patruno, Savino F. A., Michelone, Giuseppe, Gulminetti, Roberto, Zanaboni, Domenico, Novati, Stefano, Maserati, Renato, Orsolini, Paolo, Vecchia, Marco, Sciarra, Marco, Asperges, Erika, Di Filippo, Alessandro, Biscarini, Simona, Lupi, Matteo, Pieri, Teresa C., Sachs, Michele, Valsecchi, Pietro, Perlini, Stefano, Alfano, Claudia, Bonzano, Marco, Briganti, Federica, Crescenzi, Giuseppe, Falchi, Anna G., Guarnone, Roberta, Guglielmana, Barbara, Maggi, Elena, Martino, Ilaria, Pettenazza, Pietro, Pioli di Marco, Serena, Quaglia, Federica, Sabena, Anna, Salinaro, Francesco, Speciale, Francesco, Zunino, Ilaria, De Lorenzo, Marzia, Secco, Gianmarco, Dimitry, Lorenzo, Cappa, Giovanni, Maisak, Igor, Chiodi, Benedetta, Sciarrini, Massimiliano, Barcella, Bruno, Resta, Flavia, Moroni, Luca, Vezzoni, Giulia, Scattaglia, Lorenzo, Boscolo, Elisa, Zattera, Caterina, Fidel, Tassi M., Vincenzo, Capozza, Vignaroli, Damiano, Bazzini, Marco, Iotti, Giorgio, Mojoli, Francesco, Belliato, Mirko, Perotti, Luciano, Mongodi, Silvia, Tavazzi, Guido, Marseglia, Gianluigi, Licari, Amelia, Brambilla, Ilaria, Daniela, Barbarini, Antonella, Bruno, Patrizia, Cambieri, Giulia, Campanini, Giuditta, Comolli, Marta, Corbella, Rossana, Daturi, Milena, Furione, Bianca, Mariani, Roberta, Maserati, Enza, Monzillo, Stefania, Paolucci, Maurizio, Parea, Elena, Percivalle, Antonio, Piralla, Francesca, Rovida, Antonella, Sarasini, Maurizio, Zavattoni, Guy, Adzasehoun, Laura, Bellotti, Ermanna, Cabano, Giuliana, Casali, Luca, Dossena, Gabriella, Frisco, Gabriella, Garbagnoli, Alessia, Girello, Viviana, Landini, Claudia, Lucchelli, Valentina, Maliardi, Simona, Pezzaia, Marta, Premoli, Alice, Bonetti, Giacomo, Caneva, Irene, Cassaniti, Alfonso, Corcione, Di Martino, Raffella, Di Napoli, Annapia, Alessandro, Ferrari, Guglielmo, Ferrari, Loretta, Fiorina, Federica, Giardina, Alessandra, Mercato, Federica, Novazzi, Giacomo, Ratano, Beatrice, Rossi, Maria, Sciabica I., Monica, Tallarita, Edoardo, Vecchio N., Cerino, Antonella, Varchetta, Stefania, Oliviero, Barbara, Mantovani, Stefania, Mele, Dalila, Calvi, Monica, Tizzonis, Michela, Nicora, Carlo, Triarico, Antonio, Petronella, Vincenzo, Marena, Carlo, Muzzi, Alba, Lago, Paolo, Comandatore, Francesco, Bissignandi, Gherard, Gaiarsa, Stefano, Rettani, Marco, and Band, Claudio

Subjects
Male, medicine.medical_specialty, ARDS, medicine.medical_treatment, infectious disease, Disease, 030230 surgery, clinical research/practice, Asymptomatic, Tacrolimus, Kidney Failure, 03 medical and health sciences, Betacoronavirus, 0302 clinical medicine, Glomerulonephritis, medicine, Extracorporeal membrane oxygenation, Immunology and Allergy, immunosuppressant – calcineurin inhibitor: tacrolimus, infection and infectious agents – viral, COVID-19, Ceftriaxone, Coronavirus Infections, Cytokines, Glomerulonephritis, IGA, Humans, Immunosuppression Therapy, Kidney Failure, Chronic, Middle Aged, Mycophenolic Acid, Pandemics, Pneumonia, Viral, SARS-CoV-2, Treatment Outcome, Kidney Transplantation, Pharmacology (medical), Viral, Chronic, Intensive care medicine, Kidney transplantation, IGA, Mechanical ventilation, Transplantation, business.industry, Immunosuppression, Pneumonia, medicine.disease, medicine.symptom, Cytokine storm, business
Abstract

The clinical manifestation of COVID-19 can vary from an asymptomatic course to ARDS requiring invasive mechanical ventilation and extracorporeal membrane oxygenation. A kidney transplanted patient infected with SARS CoV-2 infection showed a mild disease despite immune suppression. It is possible that Immunosuppression can "be protective" as the cytokine storm is an important factor in the disease story. Despite the good outcome reported in the present case report, is remains of vital importance the solid organ transplant patients use precautions in order to avoid the infection.

Published
2020

22. An Anti-MICA/B Antibody and IL-15 Rescue Altered NKG2D-Dependent NK Cell Responses in Hepatocellular Carcinoma

Author

Mantovani, Stefania, primary, Varchetta, Stefania, additional, Mele, Dalila, additional, Donadon, Matteo, additional, Torzilli, Guido, additional, Soldani, Cristiana, additional, Franceschini, Barbara, additional, Porta, Camillo, additional, Chiellino, Silvia, additional, Pedrazzoli, Paolo, additional, Santambrogio, Roberto, additional, Barabino, Matteo, additional, Cigala, Claudia, additional, Piccolo, Gaetano, additional, Opocher, Enrico, additional, Maestri, Marcello, additional, Sangiovanni, Angelo, additional, Bernuzzi, Stefano, additional, Lhospice, Florence, additional, Kraiem, Manel, additional, Mondelli, Mario Umberto, additional, and Oliviero, Barbara, additional

Published
2020
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24. Unique immunological profile in patients with COVID-19

Author

Varchetta, Stefania, primary, Mele, Dalila, additional, Oliviero, Barbara, additional, Mantovani, Stefania, additional, Ludovisi, Serena, additional, Cerino, Antonella, additional, Bruno, Raffaele, additional, Castelli, Alberto, additional, Mosconi, Mario, additional, Vecchia, Marco, additional, Roda, Silvia, additional, Sachs, Michele, additional, Klersy, Catherine, additional, and Mondelli, Mario U., additional

Published
2020
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26. High Frequencies of Functional Virus-Specific CD4+ T Cells in SARS-CoV-2 Subjects With Olfactory and Taste Disorders.

Author

Mele, Dalila, Calastri, Anna, Maiorano, Eugenia, Cerino, Antonella, Sachs, Michele, Oliviero, Barbara, Mantovani, Stefania, Baldanti, Fausto, Bruno, Raffaele, Benazzo, Marco, Grifoni, Alba, Sette, Alessandro, Mondelli, Mario U., and Varchetta, Stefania

Subjects
SARS-CoV-2, T cells, TASTE disorders, SMELL disorders, ACUTE phase proteins, IMMUNOLOGIC diseases
Abstract

Olfactory and taste disorders (OTD) are commonly found as presenting symptoms of SARS-CoV-2 infection in patients with clinically mild COVID-19. Virus-specific T cells are thought to play an important role in the clearance of SARS-CoV-2; therefore the study of T cell specific immune responses in patients with mild symptoms may help to understand their possible role in protection from severe disease. We evaluated SARS-CoV-2-specific T cell responses to four different peptide megapools covering all SARS-CoV-2 proteins during the acute phase of the disease in 33 individuals with mild or no other symptom beside OTD and in 22 age-matched patients with severe infection. A control group of 15 outpatients with OTD and consistently negative nasopharyngeal SARS-CoV-2 RNA swabs and virus-specific IgG serology was included in the study. Increased frequencies of virus-specific CD4+ and CD8+ T cells were found in SARS-CoV-2 positive patients with OTD compared with those with severe COVID-19 and with SARS-CoV-2 negative OTD individuals. Moreover, enhanced CD4+ and CD8+ T-cell activation induced by SARS-CoV-2 peptides was associated with higher interferon (IFN)γ production. Increased frequencies of Spike (S1/S2)-specific CD4+ T cells showing enhanced IFNγ secretion and granzyme B content were associated with serum spike-specific IgG in the OTD group. In conclusion, patients with SARS-CoV-2 induced OTD develop highly functional virus-specific CD4+ and CD8+ T cells during the symptomatic phase of the disease, suggesting that robust and coordinated T-cell responses provide protection against extension of COVID-19 to the lower respiratory tract. [ABSTRACT FROM AUTHOR]

Published
2021
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29. THU-482-A human anti-MICA/B antibody boost NK cell responses in hepatocellular carcinoma

Author

MANTOVANI, STEFANIA, primary, Donadon, Matteo, additional, Soldani, Cristiana, additional, Franceschini, Barbara, additional, Santambrogio, Roberto, additional, Cigala, Claudia, additional, Maestri, Marcello, additional, Porta, Camillo, additional, Varchetta, Stefania, additional, Mele, Dalila, additional, Mondelli, Mario Umberto, additional, and Oliviero, Barbara, additional

Published
2019
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30. Deficient Natural Killer Cell NKp30‐Mediated Function and Altered NCR3 Splice Variants in Hepatocellular Carcinoma

Author

Mantovani, Stefania, primary, Oliviero, Barbara, additional, Lombardi, Andrea, additional, Varchetta, Stefania, additional, Mele, Dalila, additional, Sangiovanni, Angelo, additional, Rossi, Giorgio, additional, Donadon, Matteo, additional, Torzilli, Guido, additional, Soldani, Cristiana, additional, Porta, Camillo, additional, Pedrazzoli, Paolo, additional, Chiellino, Silvia, additional, Santambrogio, Roberto, additional, Opocher, Enrico, additional, Maestri, Marcello, additional, Bernuzzi, Stefano, additional, Rossello, Armando, additional, Clément, Sophie, additional, De Vito, Claudio, additional, Rubbia‐Brandt, Laura, additional, Negro, Francesco, additional, and Mondelli, Mario U., additional

Published
2019
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34. Lack of Siglec-7 expression identifies a dysfunctional natural killer cell subset associated with liver inflammation and fibrosis in chronic HCV infection

Author

Varchetta, Stefania, primary, Mele, Dalila, additional, Lombardi, Andrea, additional, Oliviero, Barbara, additional, Mantovani, Stefania, additional, Tinelli, Carmine, additional, Spreafico, Marta, additional, Prati, Daniele, additional, Ludovisi, Serena, additional, Ferraioli, Giovanna, additional, Filice, Carlo, additional, Aghemo, Alessio, additional, Lampertico, Pietro, additional, Facchetti, Floriana, additional, Bernuzzi, Francesca, additional, Invernizzi, Pietro, additional, and Mondelli, Mario U, additional

Published
2015
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35. Lack of Siglec-7 expression identifies a dysfunctional natural killer cell subset associated with liver inflammation and fibrosis in chronic HCV infection.

Author

Varchetta, Stefania, Mele, Dalila, Lombardi, Andrea, Oliviero, Barbara, Mantovani, Stefania, Tinelli, Carmine, Spreafico, Marta, Prati, Daniele, Ludovisi, Serena, Ferraioli, Giovanna, Filice, Carlo, Aghemo, Alessio, Lampertico, Pietro, Facchetti, Floriana, Bernuzzi, Francesca, Invernizzi, Pietro, and Mondelli, Mario U.

Subjects
CHRONIC hepatitis C, PROTEIN expression, CELL membranes, MEMBRANE proteins, FIBROSIS, PROTEOMICS
Published
2016
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36. Sialic acid-binding Ig-like lectin-7 interacts with HIV-1 gp120 and facilitates infection of CD4posT cells and macrophages

Author

Varchetta, Stefania, primary, Lusso, Paolo, additional, Hudspeth, Kelly, additional, Mikulak, Joanna, additional, Mele, Dalila, additional, Paolucci, Stefania, additional, Cimbro, Raffaello, additional, Malnati, Mauro, additional, Riva, Agostino, additional, Maserati, Renato, additional, Mondelli, Mario U, additional, and Mavilio, Domenico, additional

Published
2013
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38. Natural killer cell dynamic profile is associated with treatment outcome in patients with chronic HCV infection

Author

Oliviero, Barbara, primary, Mele, Dalila, additional, Degasperi, Elisabetta, additional, Aghemo, Alessio, additional, Cremonesi, Eleonora, additional, Rumi, Maria Grazia, additional, Tinelli, Carmine, additional, Varchetta, Stefania, additional, Mantovani, Stefania, additional, Colombo, Massimo, additional, and Mondelli, Mario U., additional

Published
2013
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40. Sialic acid-binding Ig-like lectin-7 interacts with HIV-1 gp120 and facilitates infection of CD4pos T cells and macrophages.

Author

Varchetta, Stefania, Lusso, Paolo, Hudspeth, Kelly, Mikulak, Joanna, Mele, Dalila, Paolucci, Stefania, Cimbro, Raffaello, Malnati, Mauro, Riva, Agostino, Maserati, Renato, Mondelli, Mario U., and Mavilio, Domenico

Subjects
SIALIC acids, LECTINS, HIV infections, T cells, MACROPHAGES
Abstract

Background Sialic acid-binding Ig-like lectin-7 (Siglec-7) expression is strongly reduced on natural killer (NK) cells from HIV-1 infected viremic patients. To investigate the mechanism(s) underlying this phenomenon, we hypothesized that Siglec-7 could contribute to the infection of CD4pos target cells following its interaction with HIV-1 envelope (Env) glycoprotein 120 (gp120). Results The ability of Siglec-7 to bind gp120 Env in a sialic acid-dependent manner facilitates the infection of both T cells and monocyte-derived macrophages (MDMs). Indeed, preincubation of HIV-1 with soluble Siglec-7 (sSiglec-7) increases the infection rate of CD4pos T cells, which do not constitutively express Siglec-7. Conversely, selective blockade of Siglec- 7 markedly reduces the degree of HIV-1 infection in Siglec-7pos MDMs. Finally, the sSiglec- 7 amount is increased in the serum of AIDS patients with high levels of HIV-1 viremia and inversely correlates with CD4pos T cell counts. Conclusions Our results show that Siglec-7 binds HIV-1 and contributes to enhance the susceptibility to infection of CD4pos T cells and MDMs. This phenomenon plays a role in HIV-1 pathogenesis and in disease progression, as suggested by the inverse correlation between high serum level of sSiglec-7 and the low CD4pos T cell count observed in AIDS patients in the presence of chronic viral replication. [ABSTRACT FROM AUTHOR]

Published
2013
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41. High Frequencies of Functional Virus-Specific CD4 + T Cells in SARS-CoV-2 Subjects With Olfactory and Taste Disorders.

Author

Mele D, Calastri A, Maiorano E, Cerino A, Sachs M, Oliviero B, Mantovani S, Baldanti F, Bruno R, Benazzo M, Grifoni A, Sette A, Mondelli MU, and Varchetta S

Subjects
Antibodies, Viral immunology, CD4 Lymphocyte Count, COVID-19 immunology, COVID-19 pathology, Cytokines blood, Humans, Interferon-gamma blood, Interferon-gamma immunology, Spike Glycoprotein, Coronavirus immunology, Ageusia pathology, Anosmia pathology, Antibodies, Viral blood, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, SARS-CoV-2 immunology
Abstract

Olfactory and taste disorders (OTD) are commonly found as presenting symptoms of SARS-CoV-2 infection in patients with clinically mild COVID-19. Virus-specific T cells are thought to play an important role in the clearance of SARS-CoV-2; therefore the study of T cell specific immune responses in patients with mild symptoms may help to understand their possible role in protection from severe disease. We evaluated SARS-CoV-2-specific T cell responses to four different peptide megapools covering all SARS-CoV-2 proteins during the acute phase of the disease in 33 individuals with mild or no other symptom beside OTD and in 22 age-matched patients with severe infection. A control group of 15 outpatients with OTD and consistently negative nasopharyngeal SARS-CoV-2 RNA swabs and virus-specific IgG serology was included in the study. Increased frequencies of virus-specific CD4 + and CD8 + T cells were found in SARS-CoV-2 positive patients with OTD compared with those with severe COVID-19 and with SARS-CoV-2 negative OTD individuals. Moreover, enhanced CD4 + and CD8 + T-cell activation induced by SARS-CoV-2 peptides was associated with higher interferon (IFN)γ production. Increased frequencies of Spike (S1/S2)-specific CD4 + T cells showing enhanced IFNγ secretion and granzyme B content were associated with serum spike-specific IgG in the OTD group. In conclusion, patients with SARS-CoV-2 induced OTD develop highly functional virus-specific CD4 + and CD8 + T cells during the symptomatic phase of the disease, suggesting that robust and coordinated T-cell responses provide protection against extension of COVID-19 to the lower respiratory tract., Competing Interests: AS is a consultant for Gritstone, Flow Pharma, Arcturus, Immunoscape, 20 CellCarta, OxfordImmunotech and Avalia. The remaining 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 © 2021 Mele, Calastri, Maiorano, Cerino, Sachs, Oliviero, Mantovani, Baldanti, Bruno, Benazzo, Grifoni, Sette, Mondelli and Varchetta.)

Published
2021
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42. Monocytes inhibit hepatitis C virus-induced TRAIL expression on CD56 bright NK cells.

Author

Mele D, Mantovani S, Oliviero B, Grossi G, Lombardi A, Mondelli MU, and Varchetta S

Subjects
Adult, Aged, Aged, 80 and over, Cytokines blood, Female, Humans, Intercellular Signaling Peptides and Proteins blood, Male, Middle Aged, Receptors, Interleukin antagonists & inhibitors, Virus Replication, CD56 Antigen analysis, Hepacivirus physiology, Killer Cells, Natural immunology, Monocytes physiology, TNF-Related Apoptosis-Inducing Ligand analysis
Abstract

Background & Aims: Natural killer (NK) cells play an important role in the pathogenesis of hepatitis C virus (HCV) infection. We have previously shown that culture-derived HCV (HCVcc) enhance tumor necrosis-factor-related apoptosis-inducing ligand (TRAIL) expression on healthy NK cells, but not on those from patients infected with HCV, which was likely dependent on accessory cells. Here we sought to elucidate the mechanisms involved in altered TRAIL upregulation in this setting., Methods: Peripheral blood mononuclear cells (PBMC) from controls and patients infected with HCV were exposed to HCVcc. Cell depletions were performed to identify cells responsible for NK cell activation. Flow cytometry and ELISA were used to identify the cytokines involved in the NK activation process., Results: In patients infected with HCV, soluble factors secreted by control PBMC restored the ability of NK cells to express TRAIL. Of note, CD14+ cell depletion had identical effects upon virus exposure and promoted increased degranulation. Moreover, increased concentrations of interleukin (IL)-18 binding protein a (IL-18BPa) and IL-36 receptor antagonist (IL-36RA) were observed after PBMC exposure to HCVcc in patients with HCV. HCVcc-induced NK cell TRAIL expression was inhibited by IL-18BPa and IL-36RA in control subjects. There were statistically significant correlations between IL-18BPa and indices of liver inflammation and fibrosis, supporting a role for this protein in the pathogenesis of chronic HCV infection., Conclusions: During chronic HCV infection, monocytes play a key role in negative regulation of NK cell activation, predominantly via secretion of inhibitors of IL-18 and IL-36., Lay Summary: Coordination and collaboration between immune cells are essential to fight pathogens. Herein we show that during HCV infection monocytes secrete IL-18 and IL-36 inhibitory proteins, reducing NK cell activation, and consequently inhibiting their ability to express TRAIL and kill target cells., (Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Published
2017
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