title: Acute ileitis facilitates infection with multidrug resistantPseudomonas aeruginosain human microbiota-associated mice.
abstract: BACKGROUND
  The rising incidence of multidrug resistant (MDR) Gram-negative bacteria includingPseudomonas aeruginosahas 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 facilitateP. aeruginosainfection of vertebrate hosts.
  
  
  RESULTS
  To address this, we analysedP. aeruginosainfection in human microbiota-associated (hma) mice with acute ileitis induced by peroralToxoplasma gondiichallenge. When perorally infected withP. aeruginosaat day 3 post ileitis induction, hma mice displayed higher intestinalP. aeruginosaloads as compared to hma mice without ileitis. However, the overall intestinal microbiota composition was not disturbed byP. 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 ofP. aeruginosainfected and uninfected hma mice with ileitis. The anti-inflammatory cytokine IL-10 increased multifold upon ileitis induction, but interestingly more distinctly inP. aeruginosainfected 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. aeruginosainfection 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 bloodof P. aeruginosainfected than uninfected mice at day 7 following ileitis induction,P. aeruginosainfection did not exacerbate systemic pro-inflammatory sequelae, but resulted in lower IL-10 serum levels.
  
  
  CONCLUSIONS
  Acute intestinal inflammation facilitates infection of the vertebrate host with MDR bacteria includingP. aeruginosaand might also pose particularly hospitalized patients at risk for acquisition. Since acuteT. gondiiinduced inflammation might mask immunopathology caused byP. aeruginosa, a subacute or chronic inflammation model might be better suited to investigate the potential role ofP. aeruginosainfection in the aggravation of intestinal disease.
authors.affiliation: Department of Microbiology and Hygiene, Charité-University Medicine Berlin, CC5, Campus Benjamin Franklin, FEM, Garystr. 5, 14195 Berlin, Germany.
authors.forename: Eliane
authors.initials: E
authors.lastname: von Klitzing
authors.affiliation: Department of Microbiology and Hygiene, Charité-University Medicine Berlin, CC5, Campus Benjamin Franklin, FEM, Garystr. 5, 14195 Berlin, Germany.
authors.forename: Ira
authors.initials: I
authors.lastname: Ekmekciu
authors.affiliation: Department of Microbiology and Hygiene, Charité-University Medicine Berlin, CC5, Campus Benjamin Franklin, FEM, Garystr. 5, 14195 Berlin, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bereswill
authors.affiliation: Department of Microbiology and Hygiene, Charité-University Medicine Berlin, CC5, Campus Benjamin Franklin, FEM, Garystr. 5, 14195 Berlin, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Heimesaat
keywords: Bacterial translocation; Extra-intestinal and systemic sequelae of infection; Fecal transplantation; Human microbiota-associated mice; Intestinal microbiota; Multidrug resistant Gram-negative bacteria; Pro-inflammatory immune responses; Pseudomonas aeruginosa; Susceptibility to infection; Toxoplasma gondii induced acute ileitis