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• W2130743035 abstract "Inducing long-term protective memory CD8(+) T-cells is a desirable goal for vaccines against intracellular pathogens. However, the mechanisms of differentiation of CD8(+) T-cells into long-lived memory cells capable of mediating protection of immunized hosts remain incompletely understood. We have developed an experimental system using mice immunized with wild type (WT) or mutants of the intracellular bacterium Listeria monocytogenes (Lm) that either do or do not develop protective memory CD8(+) T-cells. We previously reported that mice immunized with Lm lacking functional SecA2, an auxiliary secretion system of gram-positive bacteria, did not differentiate functional memory CD8(+) T-cells that protected against a challenge infection with WT Lm. Herein we hypothesized that the p60 and NamA autolysins of Lm, which are major substrates of the SecA2 pathway, account for this phenotype. We generated Lm genetically deficient for genes encoding for the p60 and NamA proteins, ΔiapΔmurA Lm, and further characterized this mutant. Δp60ΔNamA Lm exhibited a strong filamentous phenotype, inefficiently colonized host tissues, and grew mostly outside cells. When Δp60ΔNamA Lm was made single unit, cell invasion was restored to WT levels during vaccination, yet induced memory T-cells still did not protect immunized hosts against recall infection. Recruitment of blood phagocytes and antigen-presenting cell activation was close to that of mice immunized with ΔActA Lm, which develop protective memory. However, key inflammatory factors involved in optimal T-cell programming such as IL-12 and type I IFN (IFN-I) were lacking, suggesting that cytokine signals may largely account for the observed phenotype. Thus, altogether, these results establish that p60 and NamA secreted by Lm promote primary host cell invasion, the inflammatory response and the differentiation of functional memory CD8(+) T-cells, by preventing Lm filamentation during growth and subsequent triggering of innate sensing mechanisms." @default.
• W2130743035 created "2016-06-24" @default.
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• W2130743035 date "2014-10-31" @default.
• W2130743035 modified "2023-09-27" @default.
• W2130743035 title "The p60 and NamA autolysins from<i>L</i><i>isteria monocytogenes</i>contribute to host colonization and induction of protective memory" @default.
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• W2130743035 doi "https://doi.org/10.1111/cmi.12362" @default.
• W2130743035 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4457399" @default.
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• W2130743035 hasPublicationYear "2014" @default.
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