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 (Psae) as serious threat to human health. We here addressed whether chronic murine gut inflammation facilitates intestinal MDR Psae colonization and whether bacterial infection subsequently worsens colonic immunopathology. Converse to wildtype counterparts, Psae colonized the intestines of IL-10-/- mice with chronic colitis following peroral challenge, but did not lead to changes in intestinal microbiota composition. Psae 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-γ in mesenteric lymph nodes of Psae-infected as compared to unchallenged IL-10-/- mice. Remarkably, Psae-induced pro-inflammatory immune responses were not restricted to the gut, but could also be observed systemically as indicated by increased TNF and IFN-γ concentrations in sera upon Psae-infection. Furthermore, viable commensals originating from the intestinal microbiota translocated to extra-intestinal compartments such as liver, kidney and spleen of Psae-infected IL-10-/- mice with chronic colitis only. Hence, peroral MDR Psae-infection results in exacerbated colonic as well as systemic pro-inflammatory immune responses during chronic murine colitis.