Multidrug-resistant Pseudomonas aeruginosa aggravates inflammatory responses in murine chronic colitis

Abstract

The World Health Organization has rated multidrug-resistant (MDR) Gram-negative bacteria including Pseudomonas aeruginosa (Ps alpha e) as serious threat to human health. We here addressed whether chronic murine gut inflammation facilitates intestinal MDR Ps alpha e colonization and whether bacterial infection subsequently worsens colonic immunopathology. Converse to wildtype counterparts, Ps alpha e colonized the intestines of IL-10(-/-) mice with chronic colitis following peroral challenge, but did not lead to changes in intestinal microbiota composition. Ps alpha e infection accelerated both macroscopic (i.e. clinical) and microscopic disease (i.e. colonic epithelial apoptosis), that were accompanied by increased intestinal pro-inflammatory immune responses as indicated by elevated colonic numbers of innate and adaptive immune cell subsets and enhanced secretion of pro-inflammatory cytokines such as TNF and IFN-gamma in mesenteric lymph nodes of Ps alpha e-infected as compared to unchallenged IL-10(-/-) mice. Remarkably, Ps alpha e-induced pro-inflammatory immune responses were not restricted to the gut, but could also be observed systemically as indicated by increased TNF and IFN-gamma concentrations in sera upon Ps alpha e-infection. Furthermore, viable commensals originating from the intestinal microbiota translocated to extra-intestinal compartments such as liver, kidney and spleen of Ps alpha e-infected IL-10(-/-) mice with chronic colitis only. Hence, peroral MDR Ps alpha e-infection results in exacerbated colonic as well as systemic pro-inflammatory immune responses during chronic murine colitis.