Open AccessViral PB1-F2 and host IFN-γ guide ILC2 and T cell activity during influenza virus infection
Author(s) -
Tarani Kanta Barman,
Victor C. Huber,
Jesse L. Bonin,
Danielle Califano,
Sharon L. Salmon,
Andrew N. J. McKenzie,
Dennis W. Metzger
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2118535119
Subject(s) - biology , virulence , virus , pathogen , influenza a virus , interferon , virology , immunity , microbiology and biotechnology , host (biology) , immune system , immunology , gene , ecology , biochemistry
Significance The regulation of functional immune cell plasticity is poorly understood. Host environmental cues are critical, but the possible influence of pathogen-derived virulence factors has not been described. We have used reverse-engineered influenza A viruses that differ in PB1-F2 activity to analyze influenza in mice in the presence or absence of host interferon (IFN)-γ. In the absence of functional PB1-F2 and IFN-γ, lung ILC2s initiated robust IL-5 responses following viral challenge, which led to improved tissue integrity and survival. Conversely, functional PB1-F2 suppressed IL-5+ ILC2 responses and induced a dominant IL-13+ CD8 T cell response regardless of host IFN-γ. These findings demonstrate the critical interplay between the viral virulence factors and host cytokines in regulating protective pulmonary immunity during influenza virus infection.