Acute ileitis facilitates infection with multidrug resistant Pseudomonas aeruginosa in human microbiota-associated mice
Creators: name: Von Klitzing, Eliane
name: Ekmekciu, Ira
name: Bereswill, Stefan
name: Heimesaat, Markus M.
Publisher: name: Charité - Universitätsmedizin Berlin
Year: 2017
Subjects: subject: Bacterial translocation
subject: Extra-intestinal and systemic sequelae of infection
subject: Pro-inflammatory immune responses
subject: Toxoplasma gondii induced acute ileitis
subject: Human microbiota-associated mice
subject: Fecal transplantation
subject: Intestinal microbiota
subject: Susceptibility to infection
subject: Multidrug resistant Gram-negative bacteria
subject: Pseudomonas aeruginosa
subject: 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit

description: Background The rising incidence of multidrug resistant (MDR) Gram-negative bacteria including Pseudomonas aeruginosa has become a serious issue in prevention of its spread particularly among hospitalized patients. It is, however, unclear whether distinct conditions such as acute intestinal inflammation facilitate P. aeruginosa infection of vertebrate hosts. Methods and results To address this, we analysed P. aeruginosa infection in human microbiota-associated (hma) mice with acute ileitis induced by peroral Toxoplasma gondii challenge. When perorally infected with P. aeruginosa at day 3 post ileitis induction, hma mice displayed higher intestinal P. aeruginosa loads as compared to hma mice without ileitis. However, the overall intestinal microbiota composition was not disturbed by P. aeruginosa (except for lowered bifidobacterial populations), and the infection did not further enhance ileal immune cell responses. Pro-inflammatory cytokines including IFN-γ and IL-12p70 were similarly increased in ileum and mesenteric lymph nodes of P. aeruginosa infected and uninfected hma mice with ileitis. The anti-inflammatory cytokine IL-10 increased multifold upon ileitis induction, but interestingly more distinctly in P. aeruginosa infected as compared to uninfected controls. Immune responses were not restricted to the intestines as indicated by elevated pro-inflammatory cytokine levels in liver and kidney upon ileitis induction. However, except for hepatic TNF-α levels, P. aeruginosa infection did not result in more distinct pro-inflammatory cytokine secretion in liver and kidney of hma mice with ileitis. Whereas viable intestinal bacteria were more frequently detected in systemic compartments such as spleen and cardiac blood of P. aeruginosa infected than uninfected mice at day 7 following ileitis induction, P. aeruginosa infection did not exacerbate systemic pro- inflammatory sequelae, but resulted in lower IL-10 serum levels. Conclusion Acute intestinal inflammation facilitates infection of the vertebrate host with MDR bacteria including P. aeruginosa and might also pose particularly hospitalized patients at risk for acquisition. Since acute T. gondii induced inflammation might mask immunopathology caused by P. aeruginosa, a subacute or chronic inflammation model might be better suited to investigate the potential role of P. aeruginosa infection in the aggravation of intestinal disease