title: Influenza A virus-induced release of interleukin-10 inhibits the anti-microbial activities of invariant natural killer T cells during invasive pneumococcal superinfection.
abstract: During influenza A virus (IAV) infection, changes in the lung's physical and immunological defenses predispose the host to bacterial superinfections. Invariant natural killer T (iNKT) cells are innate-like T lymphocytes that have beneficial or harmful functions during infection. We investigated the iNKT cells' role in a model of invasive pneumococcal superinfection. The use of Jα18-/-mice indicated that iNKT cells limited susceptibility to influenza-pneumococcal infection and reduced the lethal synergism. This role did not depend on immune-based anti-bacterial mechanisms. At the time of bacterial exposure, iNKT cells from IAV-experienced mice failed to produce antipneumococcal interferon-γ and adoptive transfer of fresh iNKT cells before Streptococcus pneumoniae challenge did not restore anti-bacterial host defenses. Impaired iNKT cell activation in superinfected animals was related to the IAV-induced immunosuppressive cytokine interleukin-10 (IL-10), rather than to an intrinsic functional defect. IL-10 dampened the activation of iNKT cells in response to pneumococci by inhibiting the production of IL-12 by pulmonary monocyte-derived dendritic cells. Neutralization of IL-10 restored iNKT cell activation and tends to increase resistance to secondary bacterial infection. Overall, iNKT cells have a beneficial role (upstream of bacterial colonization) in controlling influenza-pneumococcal superinfection, although they represent novel targets of immunosuppression at the time of bacterial challenge.
authors.affiliation: Université de Lille, U1019-UMR 8204-CIIL-Centre d'Infection et d'Immunité de Lille, Lille, France.|CNRS, UMR 8204, Lille, France.|Inserm, U1019, Lille, France.|CHU Lille, Lille, France.|Institut Pasteur de Lille, Lille, France.
authors.forename: A
authors.initials: A
authors.lastname: Barthelemy
authors.affiliation: Université de Lille, U1019-UMR 8204-CIIL-Centre d'Infection et d'Immunité de Lille, Lille, France.|CNRS, UMR 8204, Lille, France.|Inserm, U1019, Lille, France.|CHU Lille, Lille, France.|Institut Pasteur de Lille, Lille, France.
authors.forename: S
authors.initials: S
authors.lastname: Ivanov
authors.affiliation: Université de Lille, U1019-UMR 8204-CIIL-Centre d'Infection et d'Immunité de Lille, Lille, France.|CNRS, UMR 8204, Lille, France.|Inserm, U1019, Lille, France.|CHU Lille, Lille, France.|Institut Pasteur de Lille, Lille, France.
authors.forename: J
authors.initials: J
authors.lastname: Fontaine
authors.affiliation: Université de Lille, U1019-UMR 8204-CIIL-Centre d'Infection et d'Immunité de Lille, Lille, France.|CNRS, UMR 8204, Lille, France.|Inserm, U1019, Lille, France.|CHU Lille, Lille, France.|Institut Pasteur de Lille, Lille, France.
authors.forename: D
authors.initials: D
authors.lastname: Soulard
authors.affiliation: Babraham Institute, Cambridge, UK.
authors.forename: H
authors.initials: H
authors.lastname: Bouabe
authors.affiliation: Université de Lille, U1019-UMR 8204-CIIL-Centre d'Infection et d'Immunité de Lille, Lille, France.|CNRS, UMR 8204, Lille, France.|Inserm, U1019, Lille, France.|CHU Lille, Lille, France.|Institut Pasteur de Lille, Lille, France.
authors.forename: C
authors.initials: C
authors.lastname: Paget
authors.affiliation: Université de Lille, U1019-UMR 8204-CIIL-Centre d'Infection et d'Immunité de Lille, Lille, France.|CNRS, UMR 8204, Lille, France.|Inserm, U1019, Lille, France.|CHU Lille, Lille, France.|Institut Pasteur de Lille, Lille, France.
authors.forename: C
authors.initials: C
authors.lastname: Faveeuw
authors.affiliation: Université de Lille, U1019-UMR 8204-CIIL-Centre d'Infection et d'Immunité de Lille, Lille, France.|CNRS, UMR 8204, Lille, France.|Inserm, U1019, Lille, France.|CHU Lille, Lille, France.|Institut Pasteur de Lille, Lille, France.
authors.forename: F
authors.initials: F
authors.lastname: Trottein
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D004198:Disease Susceptibility; D007108:Immune Tolerance; D007113:Immunity, Innate; D009980:Influenza A virus / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D011008:Pneumococcal Infections / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013296:Streptococcus pneumoniae / Q000276:immunology*; D015163:Superinfection
chemical_list: D057134:Antibodies, Neutralizing; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016753:Interleukin-10; D018664:Interleukin-12