Reynolds Lisa A, Redpath Stephen A, Yurist-Doutsch Sophie, Gill Navkiran, Brown Eric M, van der Heijden Joris, Brosschot Tara P, Han Jun, Marshall Natalie C, Woodward Sarah E, Valdez Yanet, Borchers Christoph H, Perona-Wright Georgia, Finlay B Brett
Michael Smith Laboratories, University of British Columbia, Vancouver.
Department of Biochemistry and Microbiology, University of Victoria, British Columbia.
J Infect Dis. 2017 Apr 15;215(8):1245-1254. doi: 10.1093/infdis/jix141.
Intestinal helminth infections occur predominantly in regions where exposure to enteric bacterial pathogens is also common. Helminth infections inhibit host immunity against microbial pathogens, which has largely been attributed to the induction of regulatory or type 2 (Th2) immune responses. Here we demonstrate an additional 3-way interaction in which helminth infection alters the metabolic environment of the host intestine to enhance bacterial pathogenicity. We show that an ongoing helminth infection increased colonization by Salmonella independently of T regulatory or Th2 cells. Instead, helminth infection altered the metabolic profile of the intestine, which directly enhanced bacterial expression of Salmonella pathogenicity island 1 (SPI-1) genes and increased intracellular invasion. These data reveal a novel mechanism by which a helminth-modified metabolome promotes susceptibility to bacterial coinfection.
肠道蠕虫感染主要发生在接触肠道细菌病原体也很常见的地区。蠕虫感染会抑制宿主对微生物病原体的免疫力，这在很大程度上归因于调节性或2型（Th2）免疫反应的诱导。在这里，我们展示了一种额外的三方相互作用，即蠕虫感染会改变宿主肠道的代谢环境，从而增强细菌的致病性。我们发现，持续的蠕虫感染会独立于T调节细胞或Th2细胞增加沙门氏菌的定植。相反，蠕虫感染改变了肠道的代谢谱，直接增强了沙门氏菌致病岛1（SPI-1）基因的细菌表达，并增加了细胞内入侵。这些数据揭示了一种新机制，即蠕虫修饰的代谢组促进了对细菌合并感染的易感性。
