The inflammatory cytokine tumor necrosis factor modulates the expression of Salmonella typhimurium effector proteins.
Tumor necrosis factor alpha (TNF-alpha)is a host inflammatory factor. Bacteria increase TNF-alpha expression in a variety of human diseases including infectious diseases, inflammatory bowel diseases, and cancer. It is unknown, however, how TNF-alpha directly modulates bacterial protein expression during intestinal infection and chronic inflammation. In the current study, we hypothesize that Salmonella typhimurium senses TNF-alpha and show that TNF-alpha treatment modulates Salmonella virulent proteins (called effectors), thus changing the host-bacterial interaction in intestinal epithelial cells. We investigated the expression of 23 Salmonella effectors after TNF-alpha exposure. We found that TNF-alpha treatment led to differential effector expression: effector SipA was increased by TNF-alpha treatment, whereas the expression levels of other effectors, including gogB and spvB, decreased in the presence of TNF-alpha. We verified the protein expression of Salmonella effectors AvrA and SipA by Western blots. Furthermore, we used intestinal epithelial cells as our experimental model to explore the response of human intestinal cells to TNF-alpha pretreated Salmonella. More bacterial invasion was found in host cells colonized with Salmonella strains pretreated with TNF-alpha compared to Salmonella without TNF-alpha treatment. TNF-alpha pretreated Salmonella induced higher proinflammatory JNK signalling responses compared to the Salmonella strains without TNF-alpha exposure. Exposure to TNF-alpha made Salmonella to induce more inflammatory cytokine IL-8 in intestinal epithelial cells. JNK inhibitor treatment was able to suppress the effects of TNF-pretreated-Salmonella in enhancing expressions of phosphorylated-JNK and c-jun and secretion of IL-8. Overall, our study provides new insights into Salmonella-host interactions in intestinal inflammation.
Ma
Jun
J
Department of Medicine, Gastroenterology & Hepatology Division, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Zhang
Yong-Guo
YG
Department of Medicine, Gastroenterology & Hepatology Division, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Xia
Yinglin
Y
Department of Biostatistics and Computational Biology, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Sun
Jun
J
Department of Medicine, Gastroenterology & Hepatology Division, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA.|Department of Microbiology and Immunology, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA.|James Wilmot Cancer Center, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA.