tetano
Editor, Senior Moderator
Mucosal Immunol. 2016 May 25. doi: 10.1038/mi.2016.49. [Epub ahead of print]
[h=1]Influenza A virus-induced release of interleukin-10 inhibits the anti-microbial activities of invariant natural killer T cells during invasive pneumococcal superinfection.[/h] Barthelemy A[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Ivanov S[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Fontaine J[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Soulard D[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Bouabe H[SUP]6[/SUP], Paget C[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Faveeuw C[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Trottein F[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]-/-[/SUP] 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.Mucosal Immunology advance online publication 25 May 2016. doi:10.1038/mi.2016.49.
PMID: 27220813 [PubMed - as supplied by publisher]
[h=1]Influenza A virus-induced release of interleukin-10 inhibits the anti-microbial activities of invariant natural killer T cells during invasive pneumococcal superinfection.[/h] Barthelemy A[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Ivanov S[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Fontaine J[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Soulard D[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Bouabe H[SUP]6[/SUP], Paget C[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Faveeuw C[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Trottein F[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]-/-[/SUP] 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.Mucosal Immunology advance online publication 25 May 2016. doi:10.1038/mi.2016.49.
PMID: 27220813 [PubMed - as supplied by publisher]