Salmonella Typhimurium Type III Secretion Effectors Stimulate Innate Immune Responses in Cultured Epithelial Cells

PLoS Pathogens

Richard A. Flavell¹  Steven H. Kleinstein²  María Lara-Tejero³  Vincent M. Bruno³  Jorge E. Galán³  Sebastian Hannemann³ 

[1] Department of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, United States of America;Department of Pathology and Interdepartmental Program in Computational Biology and Bioinformatics, Yale University School of Medicine, New Haven, Connecticut, United States of America;Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, United States of America

关键词: Salmonella typhimurium;    Epithelial cells;    Immune response;    Immune receptors;    Gene expression;    Inflammation;    Gastrointestinal tract;    Salmonellosis;   

DOI  :  10.1371/journal.ppat.1000538

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Recognition of conserved bacterial products by innate immune receptors leads to inflammatory responses that control pathogen spread but that can also result in pathology. Intestinal epithelial cells are exposed to bacterial products and therefore must prevent signaling through innate immune receptors to avoid pathology. However, enteric pathogens are able to stimulate intestinal inflammation. We show here that the enteric pathogen Salmonella Typhimurium can stimulate innate immune responses in cultured epithelial cells by mechanisms that do not involve receptors of the innate immune system. Instead, S. Typhimurium stimulates these responses by delivering through its type III secretion system the bacterial effector proteins SopE, SopE2, and SopB, which in a redundant fashion stimulate Rho-family GTPases leading to the activation of mitogen-activated protein (MAP) kinase and NF-κB signaling. These observations have implications for the understanding of the mechanisms by which Salmonella Typhimurium induces intestinal inflammation as well as other intestinal inflammatory pathologies.

【 授权许可】

CC BY