The p60 and NamA autolysins from Listeria monocytogenes contribute to host colonization and induction of protective memory. (31st October 2014)

• Record Type: Journal Article
• Authors: Chandrabos, Ceena; M'Homa Soudja, Saïdi; Weinrick, Brian; Gros, Marilyn; Frangaj, Aurel; Rahmoun, Massilva; Jacobs, William R.; Lauvau, Grégoire
• Is Part Of: Cellular microbiology. Volume 17:Number 2(2015:Feb.)
• Page Start: 147
• Page End: 163
• Publication Date: 2014-10-31
• Subjects: Microbiology -- Periodicals; Cytology -- Periodicals; Host-parasite relationships -- Periodicals; Microbiology -- Periodicals; Cells -- Periodicals; Microbiologie -- Périodiques; Microbiologie; Relation hôte-parasite; Cytologie; Cellule; Réponse cellulaire; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); 579.05
• DOI: 10.1111/cmi.12362
• Languages: English
• ISSNs: 1462-5814

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>Inducing long‐term protective memory CD8<sup>+</sup> T‐cells is a desirable goal for vaccines against intracellular pathogens. However, the mechanisms of differentiation of CD8<sup>+</sup> 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 <italic>Listeria monocytogenes</italic> (<italic>Lm</italic>) that either do or do not develop protective memory CD8<sup>+</sup> T‐cells. We previously reported that mice immunized with <italic>Lm</italic> lacking functional SecA2, an auxiliary secretion system of gram‐positive bacteria, did not differentiate functional memory CD8<sup>+</sup> T‐cells that protected against a challenge infection with WT <italic>Lm</italic>. Herein we hypothesized that the p60 and NamA autolysins of <italic>Lm</italic>, which are major substrates of the SecA2 pathway, account for this phenotype. We generated <italic>Lm</italic> genetically deficient for genes encoding for the p60 and NamA proteins, <italic>ΔiapΔmurA Lm</italic>, and further characterized this mutant. Δp60ΔNamA <italic>Lm</italic> exhibited a strong filamentous phenotype, inefficiently colonized host tissues, and grew mostly outside cells. When Δp60ΔNamA <italic>Lm</italic> 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 <italic>Lm</italic>, 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 <italic>Lm</italic> promote primary host cell invasion, the inflammatory response and the differentiation of functional memory CD8<sup>+</sup> T‐cells, by preventing <italic>Lm</italic> filamentation during growth and subsequent triggering of innate sensing mechanisms.</p> </abstract>