Salmonella Typhimurium type III secretion effectors stimulate innate immune responses in cultured epithelial cells.
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-kappaB 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.
Bruno
Vincent M
VM
Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.
Hannemann
Sebastian
S
Lara-Tejero
María
M
Flavell
Richard A
RA
Kleinstein
Steven H
SH
Galán
Jorge E
JE
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D003092:Colitis / Q000276:immunology / Q000382:microbiology; D004847:Epithelial Cells / Q000382:microbiology*; D015870:Gene Expression; D020869:Gene Expression Profiling; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D065636:Myotonin-Protein Kinase; D016328:NF-kappa B / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012480:Salmonella Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012486:Salmonella typhimurium / Q000276:immunology*; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic
D001426:Bacterial Proteins; D020662:Guanine Nucleotide Exchange Factors; D016328:NF-kappa B; C103987:SopE protein, Salmonella; C436324:SopE2 protein, Salmonella typhimurium; C105518:CDC42BPA protein, human; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C489224:SopB protein, Salmonella