Instead, we show that El Tor Vibrio cholerae engages the canonical Nlrp3 inflammasome for IL-1β secretion through its accessory hlyA toxin. In contrast to the Classical biotype, we here show that El Tor Vibrio cholerae induces IL-1β maturation and secretion in a caspase-11- and CT-independent manner. Previous studies demonstrated that the Classical biotype of Vibrio cholerae triggers caspase-11-dependent non-canonical inflammasome activation in macrophages following CT-mediated cytosolic delivery of LPS. While both of these biotypes express the characteristic Cholera Toxin (CT), the El Tor biotype additionally expresses the accessory toxins hemolysin (hlyA) and multifunctional auto-processing repeat-in-toxin (MARTX). Genomic Vibrio cholerae research revealed that the strains causing this ongoing cholera pandemic are members of the El Tor biotype, which fully replaced the Classical biotype that caused former cholera pandemics. Vibrio cholerae is a Gram-negative enteropathogen causing potentially life-threatening cholera disease outbreaks, for which the World Health Organization currently registers 2–4 million cases and ~100.000 cholera-associated deaths annually worldwide. 5Janssen Immunosciences, World Without Disease Accelerator, Pharmaceutical Companies of Johnson & Johnson, Beerse, Belgium.4Ghent Gut Inflammation Group (GGIG), Ghent University, Ghent, Belgium.3Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.2VIB-UGent Center for Inflammation Research, VIB, Ghent, Belgium.1Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.Frising 1,2, Tomoko Asaoka 1,2, Geert van Loo 2,3,4, Mohamed Lamkanfi 1,5 and Andy Wullaert 1,2,3,4 *
0 kommentar(er)
