Publikationsdatenbank

Attenuation of immune-mediated influenza pneumonia by targeting the inducible co-stimulator (ICOS) molecule on T cells (2014)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Sakthivel, Priya

Gereke, Marcus

Breithaupt, Angele (WE 12)

Fuchs, Dietmar

Gigliotti, Luca

Gruber, Achim D (WE 12)

Dianzani, Umberto

Bruder, Dunja

Quelle

PLOS ONE

Bandzählung: 9

Heftzählung: 7

Seiten: e100970

ISSN: 1932-6203

Sprache

Englisch

Verweise

URL (Volltext): http://edocs.fu-berlin.de/docs/receive/FUDOCS_document_000000021104

DOI: 10.1371/journal.pone.0100970

Pubmed: 25029240

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Inducible Co-stimulator (ICOS) plays a critical role in mediating T cell differentiation and function and is considered a key player in balancing T effector and T regulatory (Treg) cell responses. Here we show that activation of the ICOS signalling pathway during acute influenza A virus (IAV) infection by application of an agonistic ICOS antibody reduced the frequency of CD8+ T cells in the respiratory tract of IAV infected animals and delayed pathogen elimination. In line with this, immune-mediated influenza pneumonia was significantly ameliorated in mice that received ICOS agonist as indicated by significantly reduced alveolar infiltrations and bronchointerstitial pneumonia, while at the same time virus-related pathology remained unaffected. Importantly, ICOS agonist treatment resulted in expansion of CD4+Foxp3+ Tregs in IAV infected mice, which was associated with elevated levels of the immunosuppressive cytokine IL-10 in the alveolar space. Together, our findings suggest a prominent role of ICOS signaling during acute IAV infection by increasing the Treg/CD8+ T cell ratio with beneficial outcome on immune-mediated pneumonia and underline the suitability of ICOS as potential therapeutic target for immune intervention in those infectious conditions characterized by strong immunopathology rather than virus-mediated cytopathic effects.