Acute ileitis facilitates infection with multidrug resistant in human microbiota-associated mice.

BACKGROUND

The rising incidence of multidrug resistant (MDR) Gram-negative bacteria including 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 infection of vertebrate hosts.

METHODS AND RESULTS

To address this, we analysed infection in human microbiota-associated (hma) mice with acute ileitis induced by peroral challenge. When perorally infected with at day 3 post ileitis induction, hma mice displayed higher intestinal loads as compared to hma mice without ileitis. However, the overall intestinal microbiota composition was not disturbed by (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 infected and uninfected hma mice with ileitis. The anti-inflammatory cytokine IL-10 increased multifold upon ileitis induction, but interestingly more distinctly in 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, 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 infected than uninfected mice at day 7 following ileitis induction, 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 and might also pose particularly hospitalized patients at risk for acquisition. Since acute induced inflammation might mask immunopathology caused by , a subacute or chronic inflammation model might be better suited to investigate the potential role of infection in the aggravation of intestinal disease.