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• W4313356115 endingPage "148.24" @default.
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• W4313356115 abstract "Abstract Francisella tularensis is a highly infectious intracellular bacterium that causes the potentially fatal disease tularemia. MyD88 has previously been shown to confer protection against both attenuated and virulent strains of F. tularensis, however the underlying mechanisms of protection are largely unexplored. Here we investigated cell-specific mechanisms of protection against virulent F. tularensis infection using mice with conditional MyD88 deficiencies. MyD88 deficiency in myeloid or dendritic cells did not enhance susceptibility to F. tularensis, regardless of the route of infection. In addition, myeloid or dendritic cell MyD88 deficiency did not markedly hinder the production of inflammatory cytokines. In contrast, MyD88−/− mice, or mice with hematopoietic MyD88 deficiency display elevated bacterial burdens, and markedly reduced cytokine levels. While IL-12 levels were not diminished in MyD88−/− or hematopoietic MyD88-deficient mice infected with F. tularensis, IFN-γ production was abolished in these animals. In particular, IFN-γ production by splenic NK cells was abated in mice lacking hematopoietic MyD88. Neutralization of IFN-γ from wild-type, but not hematopoietic MyD88-deficient mice, resulted in elevated tissue F. tularensis burdens. Caspase-1/11−/− mice also displayed enhanced bacterial burdens, diminished serum IL-18 levels, and reduced IFN-γ production. Collectively, our data shows that hematopoietic MyD88 is required for IFN-γ production that is protective against F. tularensis infection. As IL-18 requires MyD88 for signaling to induce IFN-γ production, MyD88 signaling in hematopoietic cells, such as NK cells, may result in the production of protective IFN-γ via caspase1/11 dependent IL-18." @default.
• W4313356115 created "2023-01-06" @default.
• W4313356115 creator A5009868743 @default.
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• W4313356115 date "2017-05-01" @default.
• W4313356115 modified "2023-09-27" @default.
• W4313356115 title "Hematopoietic MyD88 mediates protection against virulent <i>Francisella tularensis</i> infection via IFN-γ, but does not require myeloid or dendritic cell MyD88 signaling" @default.
• W4313356115 doi "https://doi.org/10.4049/jimmunol.198.supp.148.24" @default.
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