Pivotal Advance: Invariant NKT cells reduce accumulation of inflammatory monocytes in the lungs and decrease immune-pathology during severe influenza A virus infection

Journal of Leukocyte Biology

Kambez Benam³  Wai Ling Kok³  Laura Denney³  Colin Clelland¹  Andrew J. McMichael and³  Ling-Pei Ho,²  Suzanne Cole³ 

[1]  Pathology Department, The John Radcliffe Hospital, Oxford, United Kingdom;;MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, United Kingdom; Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford, United KingdomMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, United Kingdom;

关键词: iNKT;    chemokines;    respiratory viruses;    innate immune response;    lung injury;   

DOI  :  10.1189/jlb.0411184

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Little is known of how a strong immune response in the lungs is regulated to minimize tissue injury during severe influenza A virus (IAV) infection. Here, using a model of lethal, high-pathogenicity IAV infection, we first show that Ly6ChiLy6G– inflammatory monocytes, and not neutrophils, are the main infiltrate in lungs of WT mice. Mice devoid of iNKT cells (Jα18−/− mice) have increased levels of inflammatory monocytes, which correlated with increased lung injury and mortality (but not viral load). Activation of iNKT cells correlated with reduction of MCP-1 levels and improved outcome. iNKT cells were able to selectively lyse infected, MCP-1-producing monocytes in vitro, in a CD1d-dependent process. Our study provides a detailed profile and kinetics of innate immune cells in the lungs during severe IAV infection, highlighting inflammatory monocytes as the major infiltrate and identifying a role for iNKT cells in control of these cells and lung immune-pathology.

【 授权许可】

Unknown