PI3Kγ Is Critical for Dendritic Cell-Mediated CD8+ T Cell Priming and Viral Clearance during Influenza Virus Infection

PLoS Pathogens

Jatta Huotari¹  Ari Helenius¹  Christoph Schneider²  Samuel Philip Nobs²  Manfred Kopf²  Alex Kaspar Heer² 

[1] Institute of Biochemistry, ETH Zürich, Zurich, Switzerland;Molecular Biomedicine, Institute of Molecular Health Sciences, Department of Biology, ETH Zurich, Zurich, Switzerland

关键词: T cells;    Respiratory infections;    Cytotoxic T cells;    Influenza A virus;    Influenza viruses;    Dendritic cells;    Flow cytometry;    Inflammation;   

DOI  :  10.1371/journal.ppat.1005508

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Phosphoinositide-3-kinases have been shown to be involved in influenza virus pathogenesis. They are targeted directly by virus proteins and are essential for efficient viral replication in infected lung epithelial cells. However, to date the role of PI3K signaling in influenza infection in vivo has not been thoroughly addressed. Here we show that one of the PI3K subunits, p110γ, is in fact critically required for mediating the host’s antiviral response. PI3Kγ deficient animals exhibit a delayed viral clearance and increased morbidity during respiratory infection with influenza virus. We demonstrate that p110γ is required for the generation and maintenance of potent antiviral CD8+ T cell responses through the developmental regulation of pulmonary cross-presenting CD103+ dendritic cells under homeostatic and inflammatory conditions. The defect in lung dendritic cells leads to deficient CD8+ T cell priming, which is associated with higher viral titers and more severe disease course during the infection. We thus identify PI3Kγ as a novel key host protective factor in influenza virus infection and shed light on an unappreciated layer of complexity concerning the role of PI3K signaling in this context.

【 授权许可】

CC BY