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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.
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https://hal-univ-tours.archives-ouvertes.fr/hal-03365122
Contributor : Christophe Paget Connect in order to contact the contributor
Submitted on : Tuesday, October 5, 2021 - 10:39:08 AM
Last modification on : Tuesday, October 19, 2021 - 11:56:32 PM

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A Barthelemy, S Ivanov, J Fontaine, D Soulard, H Bouabe, et al.. Influenza A virus-induced release of interleukin-10 inhibits the anti-microbial activities of invariant natural killer T cells during invasive pneumococcal superinfection. Mucosal Immunology, Nature Pub. Group, 2017, 10 (2), pp.460-469. ⟨10.1038/mi.2016.49⟩. ⟨hal-03365122⟩

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