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Media type:
E-Article
Title:
Peroral low-dose Toxoplasma gondii infection of human microbiota-associated mice — a subacute ileitis model to unravel pathogen–host interactions
Contributor:
Heimesaat, Markus M.;
Escher, Ulrike;
Grunau, Anne;
Fiebiger, Ulrike;
Bereswill, Stefan
imprint:
Akademiai Kiado Zrt., 2018
Published in:European Journal of Microbiology and Immunology
Language:
Not determined
DOI:
10.1556/1886.2018.00005
ISSN:
2062-8633
Origination:
Footnote:
Description:
<jats:p>Within 1 week following high-dose <jats:italic>Toxoplasma gondii</jats:italic> infection, mice develop lethal necrotizing ileitis. However, data from a subacute <jats:italic>T. gondii</jats:italic>-induced ileitis model are scarce. Therefore, mice harboring a human gut microbiota were perorally infected with one cyst of <jats:italic>T. gondii</jats:italic>. Within 9 days post-infection, the intestinal microbiota composition shifted towards higher loads of commensal enterobacteria and enterococci. Following <jats:italic>T. gondii</jats:italic> infection, mice were clinically only mildly affected, whereas ≈60% of mice displayed fecal blood and mild-to-moderate ileal histopathological changes. Intestinal inflammation was further characterized by increased apoptotic intestinal epithelial cells, which were accompanied by elevated proliferating gut epithelial cell numbers. As compared to naive controls, infected mice displayed elevated numbers of intestinal T lymphocytes and regulatory T-cells and increased pro-inflammatory mediator secretion. Remarkably, <jats:italic>T. gondii</jats:italic>-induced apoptotic and pro-inflammatory immune responses were not restricted to the gut, but could also be observed in extra-intestinal compartments including kidney, liver, and lung. Strikingly, low-dose <jats:italic>T. gondii</jats:italic> infection resulted in increased serum levels of pro- and anti-inflammatory cytokines. In conclusion, the here presented subacute ileitis model following peroral low-dose <jats:italic>T. gondii</jats:italic> infection of humanized mice allows for detailed investigations of the molecular mechanism underlying the “ménage à trois” of pathogens, human gut microbiota, and immunity.</jats:p>