title: Pivotal Advance: Invariant NKT cells reduce accumulation of inflammatory monocytes in the lungs and decrease immune-pathology during severe influenza A virus infection.
abstract: 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 (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.
authors: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK.
authors: Wai Ling
authors: WL
authors: Kok
authors: Laura
authors: L
authors: Denney
authors: Kambez
authors: K
authors: Benam
authors: Suzanne
authors: S
authors: Cole
authors: Colin
authors: C
authors: Clelland
authors: Andrew J
authors: AJ
authors: McMichael
authors: Ling-Pei
authors: LP
authors: Ho
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage / Q000276:immunology; D055610:Antigens, CD1d / Q000378:metabolism; D000950:Antigens, Ly / Q000378:metabolism; D018932:Chemokine CCL2 / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009980:Influenza A virus / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D055611:Natural Killer T-Cells / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000821:virology
chemical_list: D019138:Antibodies, Blocking; D055610:Antigens, CD1d; D000950:Antigens, Ly; D018932:Chemokine CCL2