Salmonella enterica Serovar Typhi Conceals the Invasion-Associated Type Three Secretion System from the Innate Immune System by Gene Regulation

PLoS Pathogens

Geraldo E. S. Alves¹  Fabiane Cassou¹  Renato L. Santos¹  Erica A. Costa¹  Tatiane A. Paixão²  Luciana F. Costa²  Victor Poon³  Franziska Faber³  A. Marijke Keestra³  Sebastian E. Winter³  Maria G. Winter³  Torsten Sterzenbach³  Andreas J. Bäumler³ 

[1] Departamento de Clinica e Cirurgia Veterinárias, Escola de Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, United States of America

关键词: Salmonella typhi;    Salmonella typhimurium;    Transcription factors;    Inflammation;    Epithelial cells;    Gene expression;    Gastrointestinal tract;    Gene regulation;   

DOI  :  10.1371/journal.ppat.1004207

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Delivery of microbial products into the mammalian cell cytosol by bacterial secretion systems is a strong stimulus for triggering pro-inflammatory host responses. Here we show that Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, tightly regulates expression of the invasion-associated type III secretion system (T3SS-1) and thus fails to activate these innate immune signaling pathways. The S. Typhi regulatory protein TviA rapidly repressed T3SS-1 expression, thereby preventing RAC1-dependent, RIP2-dependent activation of NF-κB in epithelial cells. Heterologous expression of TviA in S. enterica serovar Typhimurium (S. Typhimurium) suppressed T3SS-1-dependent inflammatory responses generated early after infection in animal models of gastroenteritis. These results suggest that S. Typhi reduces intestinal inflammation by limiting the induction of pathogen-induced processes through regulation of virulence gene expression.

【 授权许可】

CC BY