Lung γδ T Cells Mediate Protective Responses during Neonatal Influenza Infection that Are Associated with Type 2 Immunity

Abstract

Compared to adults, infants suffer higher rates of hospitalization, severe clinical complications, and mortality due to influenza infection. We found that γδ Tcells protected neonatal mice against mortality during influenza infection. γδ Tcell deficiency did not alter viral clearance or interferon-γ production. Instead, neonatal influenza infection induced the accumulation of interleukin-17A (IL-17A)-producing γδ Tcells, which was associated with IL-33 production by lung epithelial cells. Neonates lacking IL-17A-expressing γδ Tcells or Il33 had higher mortality upon influenza infection. γδ Tcells and IL-33 promoted lung infiltration of group 2 innate lymphoid cells and regulatory Tcells, resulting in increased amphiregulin secretion and tissue repair. In influenza-infected children, IL-17A, IL-33, and amphiregulin expression were correlated, and increased IL-17A levels in nasal aspirates were associated with better clinical outcomes. Our results indicate that γδ Tcells are required in influenza-infected neonates to initiate protective immunity and mediate lung homeostasis.