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• W4380291225 abstract "Listeria monocytogenes is a facultative intracellular pathogen that has been used for decades to understand mechanisms of bacterial pathogenesis and both innate and adaptive immunity. L. monocytogenes is a potent activator of CD8+ T-cell-mediated immunity, yet how the innate immune response to infection modulates CD8+ T-cell responses is incompletely understood. Here, we address how two innate immune pathways triggered by L. monocytogenes, type I interferon (IFN) production and inflammasome activation, impact the CD8+ T-cell response. We utilized a combination of mutant mice and genetically engineered L. monocytogenes to address this question. Mice lacking the type I IFN receptor (IFNAR-/-) had the most robust T-cell response, while caspase-1-/- mice were not different from wild type (WT). Caspase-1-/-/IFNAR-/- mice had fewer T-cells than IFNAR-/- mice, suggesting a role for inflammasome activation in the absence of type I IFN. IFNAR-/- had more than twice as many memory precursors promoting enhanced protection from rechallenge. Importantly, short-lived effectors were equivalent in all strains of mice. L. monocytogenes strains genetically modified to induce lower type I interferon production yielded enhanced T-cell responses. IFNAR-/- dendritic cells induced more T-cells to proliferate than WT in ex vivo T-cell proliferation assays, suggesting deficits from type I interferon signaling may be dendritic cell intrinsic, rather than acting on T-cells. Thus, modulating type I IFN signaling during vaccination may lead to more potent T-cell-based vaccines. Importantly, this suggests innate immune signaling significantly impacts the CD8+ T-cell response and suggests CD8+ T-cell quantity and quality are important factors to consider during rational vaccine design." @default.
• W4380291225 created "2023-06-13" @default.
• W4380291225 creator A5018418164 @default.
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• W4380291225 date "2023-07-18" @default.
• W4380291225 modified "2023-09-24" @default.
• W4380291225 title "Type I Interferon Signaling on Antigen-Presenting Cells Blunts Cell-Mediated Immunity toward Listeria monocytogenes" @default.
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• W4380291225 doi "https://doi.org/10.1128/iai.00540-22" @default.
• W4380291225 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37306593" @default.
• W4380291225 hasPublicationYear "2023" @default.
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