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

2.50
Hdl Handle:
http://hdl.handle.net/10033/323399
Title:
Attenuation of immune-mediated influenza pneumonia by targeting the inducible co-stimulator (ICOS) molecule on T cells.
Authors:
Sakthivel, Priya; Gereke, Marcus; Breithaupt, Angele; Fuchs, Dietmar; Gigliotti, Luca; Gruber, Achim D; Dianzani, Umberto; Bruder, Dunja ( 0000-0003-3066-189X )
Abstract:
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.
Citation:
Attenuation of immune-mediated influenza pneumonia by targeting the inducible co-stimulator (ICOS) molecule on T cells. 2014, 9 (7):e100970 PLoS ONE
Journal:
PloS one
Issue Date:
2014
URI:
http://hdl.handle.net/10033/323399
DOI:
10.1371/journal.pone.0100970
PubMed ID:
25029240
Type:
Article
Language:
en
ISSN:
1932-6203
Appears in Collections:
publications of the research group immunoregulation (IREG)

Full metadata record

DC FieldValue Language
dc.contributor.authorSakthivel, Priyaen
dc.contributor.authorGereke, Marcusen
dc.contributor.authorBreithaupt, Angeleen
dc.contributor.authorFuchs, Dietmaren
dc.contributor.authorGigliotti, Lucaen
dc.contributor.authorGruber, Achim Den
dc.contributor.authorDianzani, Umbertoen
dc.contributor.authorBruder, Dunjaen
dc.date.accessioned2014-07-18T09:38:37Z-
dc.date.available2014-07-18T09:38:37Z-
dc.date.issued2014-
dc.identifier.citationAttenuation of immune-mediated influenza pneumonia by targeting the inducible co-stimulator (ICOS) molecule on T cells. 2014, 9 (7):e100970 PLoS ONEen
dc.identifier.issn1932-6203-
dc.identifier.pmid25029240-
dc.identifier.doi10.1371/journal.pone.0100970-
dc.identifier.urihttp://hdl.handle.net/10033/323399-
dc.description.abstractInducible 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.en
dc.language.isoenen
dc.rightsArchived with thanks to PloS oneen
dc.titleAttenuation of immune-mediated influenza pneumonia by targeting the inducible co-stimulator (ICOS) molecule on T cells.en
dc.typeArticleen
dc.identifier.journalPloS oneen

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