We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Host-derived lipids orchestrate pulmonary γδ T cell response to provide early protection against influenza virus infection.
- Authors
Wang, Xiaohui; Lin, Xiang; Zheng, Zihan; Lu, Bingtai; Wang, Jun; Tan, Andy Hee-Meng; Zhao, Meng; Loh, Jia Tong; Ng, Sze Wai; Chen, Qian; Xiao, Fan; Huang, Enyu; Ko, King-Hung; Huang, Zhong; Li, Jingyi; Kok, Kin-Hang; Lu, Gen; Liu, Xiaohui; Lam, Kong-Peng; Liu, Wanli
- Abstract
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 γδ T cells to produce interleukin 17 A (IL-17A) for early protection against H1N1 influenza infection. During infection, the lung γδ 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 γδ T (Tγδ17) cells with a phenotype of TCRγδhiCD3hiAQP3hiCXCR6hi 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 γδ T cells via γδTCR-mediated IRF4-dependent transcription. Reduced IL-17A production in γδ 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 γδ 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.
- Subjects
T cells; VIRUS diseases; INFLUENZA A virus; INFLUENZA viruses; H1N1 influenza
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-22242-9