Viral PB1-F2 and host IFN-γ guide ILC2 and T cell activity during influenza virus infection
Tarani Kanta Barman, Victor C. Huber, Jesse L. Bonin, Danielle Califano, Sharon L. Salmon, Andrew N. J. McKenzie, Dennis W. Metzger
Abstract
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.