期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 91, 期 3, 页码 357-368出版社
WILEY
DOI: 10.1189/jlb.0411184
关键词
iNKT; chemokines; respiratory viruses; innate immune response; lung injury
资金
- Medical Research Council UK
- Department of Health
- Medical Research Council [G1000800a, G0600371] Funding Source: researchfish
- National Institute for Health Research [DHCS/04/G121/68] Funding Source: researchfish
- MRC [G0600371] Funding Source: UKRI
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 Ly6C(hi)Ly6G(-)inflammatory monocytes, and not neutrophils, are the main infiltrate in lungs of WT mice. Mice devoid of iNKT cells (J alpha 18(-/-) 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. J. Leukoc. Biol. 91: 357-368; 2012.
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