title: Salmonella downregulates Nod-like receptor family CARD domain containing protein 4 expression to promote its survival in B cells by preventing inflammasome activation and cell death.
abstract: Salmonella infects and survives within B cells, but the mechanism used by the bacterium to promote its survival in these cells is unknown. In macrophages, flagellin secreted by Salmonella activates the Nod-like receptor (NLR) family CARD domain containing protein 4 (NLRC4) inflammasome, leading to the production of IL-1β and pyroptosis of infected cells. In this study, we demonstrated that the NLRC4 inflammasome is functional in B cells; however, in Salmonella-infected B cells, IL-1β secretion is prevented through the downregulation of NLRC4 expression. A functional Salmonella pathogenicity island 1 type III secretion system appears to be required for this process. Furthermore, infection induces Yap phosphorylation and promotes the interaction of Yap with Hck, thus preventing the transcriptional activation of NLRC4. The ability of Salmonella to inhibit IL-1β production also prevents B cell death; thus, B cells represent an ideal niche in which Salmonella resides, thereby promoting its persistence and dissemination.
authors.affiliation: Departamento de Biomedicina Molecular, Centro de Investigación y Estudios Avanzados del Instituto Politecnico Nacional, Mexico City CP 07360, México.
authors.forename: Araceli
authors.initials: A
authors.lastname: Perez-Lopez
authors.forename: Roberto
authors.initials: R
authors.lastname: Rosales-Reyes
authors.forename: Celia Mercedes
authors.initials: CM
authors.lastname: Alpuche-Aranda
authors.forename: Vianney
authors.initials: V
authors.lastname: Ortiz-Navarrete
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D018797:Cell Cycle Proteins; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation; D005260:Female; D005408:Flagellin / Q000494:pharmacology; D005786:Gene Expression Regulation; D057131:Immune Evasion / Q000235:genetics*; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010750:Phosphoproteins / Q000378:metabolism; D051572:Proto-Oncogene Proteins c-hck / Q000378:metabolism; D012481:Salmonella Infections, Animal / Q000235:genetics / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D014158:Transcription, Genetic; D014774:Virulence; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D001426:Bacterial Proteins; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D016207:Cytokines; D058847:Inflammasomes; D053583:Interleukin-1beta; C512299:Ipaf protein, mouse; D010750:Phosphoproteins; C419942:Spi1 protein, Salmonella; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; D005408:Flagellin; C496632:Hck protein, mouse; D051572:Proto-Oncogene Proteins c-hck