Enteropathogenic Uses NleA to Inhibit NLRP3 Inflammasome Activation

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Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) cause severe intestinal dysfunction, including watery diarrhea or severe bloody diarrhea, and acute kidney failure (hemolytic uremic syndrome). Transmitted through ingestion of contaminated food, these pathogens colonize and disrupt the linings of intestinal epithelial cells. EPEC and EHEC interrupt many cellular functions, including the inflammation response, to increase their chances of proliferation and survival in the intestine. Upon detection of the invasion, epithelial cells and immune cells secrete inflammatory cytokines to further boost the immune response for efficient clearance of the pathogens. IL-1β is an important inflammatory cytokine, and its secretion is regulated by a multimeric protein complex, termed the inflammasome, in host cells. In this study, we discovered that EPEC injects a bacterial effector protein, NleA, to inhibit the secretion of IL-1β. Exploring the potential mechanisms, we found that NleA does so by directly associating with NLRP3 (Nod-Like Receptor 3), one of the three basic components of the inflammasome, and that the presence of NleA interrupts the de-ubiquitination of NLRP3, which is a prerequisite for the assembly of the inflammasome. As a result, NleA reduces the formation of the NLRP3 inflammasome and negatively regulates the secretion of IL-1β.

Vyšlo v časopise: Enteropathogenic Uses NleA to Inhibit NLRP3 Inflammasome Activation. PLoS Pathog 11(9): e32767. doi:10.1371/journal.ppat.1005121
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005121

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