Citrobacter rodentium and Escherichia coli interactions with mucus producing colonic epithelical cells

Sammanfattning: The epithelial cells together with the mucus layer protect the host from noxious luminal substances and pathogenic invasion. Pathogens have evolved numerous strategies to circumvent these barriers and mount infection. C. rodentium is a murine model for the attaching and effacing intestinal E. coli (EPEC, EHEC) and share similar virulence strategies to infect their host. We found that the colonic mucus layer is dynamically regulated by C. rodentium and the ensuing cytokine response. The cytokine profile investigated during the course of infection indicated a shift from pro- to an anti-inflammatory type of response at times of increased mucus layer thickness. The in vitro effect of signature cytokines of pro- and anti-inflammatory responses and the pathogens (EPEC, ETEC and C. rodentium) indicated that changes in mucin production and secretion are affected by the combined impact of these factors. The anti-inflammatory cytokine IL-4 alleviated mitochondrial dysfunction in vitro and accelerated mucin production and secretion, especially in the presence of EPEC, ETEC and C. rodentium. In vivo IL-4 treatment improved mitochondria and barrier functions and colitis symptoms. Similarly, VIP alleviated mitochondrial dysfunction during infection. The lack of Fpr2 lead to decreased barrier function and increased susceptibility to C. rodentium and EPEC infection. Harnessing the host’s response to pathogens could improve the intestinal mucus barrier function by enhancing mucosal healing and shortening the duration of infection.