Host-derived lipids orchestrate pulmonary γδ T cell response to provide early protection against influenza virus infection

Innate immunity is important for host defense by eliciting rapid anti-viral responses and bridging adaptive immunity. Here, we show that endogenous lipids released from virus-infected host cells activate lung gamma delta T cells to produce interleukin 17A (IL-17A) for early protection against H1N1 influenza infection. During infection, the lung gamma delta T cell pool is constantly supplemented by thymic output, with recent emigrants infiltrating into the lung parenchyma and airway to acquire tissue-resident feature. Single-cell studies identify IL-17A-producing gamma delta T (T gamma delta 17) cells with a phenotype of TCR gamma delta (hi)CD3(hi)AQP3(hi)CXCR6(hi) in both infected mice and patients with pneumonia. Mechanistically, host cell-released lipids during viral infection are presented by lung infiltrating CD1d(+) B-1a cells to activate IL-17A production in gamma delta T cells via gamma delta TCR-mediated IRF4-dependent transcription. Reduced IL-17A production in gamma delta T cells is detected in mice either lacking B-1a cells or with ablated CD1d in B cells. Our findings identify a local host-immune crosstalk and define important cellular and molecular mediators for early innate defense against lung viral infection. Influenza A infection results in gamma delta T cell influx and production of IL-17 in the lungs. Here, the authors show that this effect is primed by CD1-restricted ligands that are released by infected cells and presented by B1a cells in the lungs.

Automated summary

Innate immunity plays a crucial role in defending against viral infections. This study demonstrates that endogenous lipids released from virus-infected host cells activate lung gamma delta T cells to produce IL-17A for early protection against H1N1 influenza infection. The interaction between host cells, B-1a cells, and gamma delta T cells defines important cellular and molecular mediators for early defense against lung viral infections.