15 research outputs found
Intestinal, extra-intestinal and systemic sequelae of Toxoplasma gondii induced acute ileitis in mice harboring a human gut microbiota
Background Within seven days following peroral high dose infection with
Toxoplasma gondii susceptible conventionally colonized mice develop acute
ileitis due to an underlying T helper cell (Th) -1 type immunopathology. We
here addressed whether mice harboring a human intestinal microbiota developed
intestinal, extra-intestinal and systemic sequelae upon ileitis induction.
Methodology/Principal findings Secondary abiotic mice were generated by broad-
spectrum antibiotic treatment and associated with a complex human intestinal
microbiota following peroral fecal microbiota transplantation. Within three
weeks the human microbiota had stably established in the murine intestinal
tract as assessed by quantitative cultural and culture-independent (i.e.
molecular 16S rRNA based) methods. At day 7 post infection (p.i.) with 50
cysts of T. gondii strain ME49 by gavage human microbiota associated (hma)
mice displayed severe clinical, macroscopic and microscopic sequelae
indicating acute ileitis. In diseased hma mice increased numbers of innate and
adaptive immune cells within the ileal mucosa and lamina propria and elevated
intestinal secretion of pro-inflammatory mediators including IFN-γ, IL-12 and
nitric oxide could be observed at day 7 p.i. Ileitis development was
accompanied by substantial shifts in intestinal microbiota composition of hma
mice characterized by elevated total bacterial loads and increased numbers of
intestinal Gram-negative commensals such as enterobacteria and Bacteroides /
Prevotella species overgrowing the small and large intestinal lumen.
Furthermore, viable bacteria translocated from the inflamed ileum to extra-
intestinal including systemic compartments. Notably, pro-inflammatory immune
responses were not restricted to the intestinal tract as indicated by
increased pro-inflammatory cytokine secretion in extra-intestinal (i.e. liver
and kidney) and systemic compartments including spleen and serum.
Conclusion/Significance With respect to the intestinal microbiota composition
“humanized” mice display acute ileitis following peroral high dose T. gondii
infection. Thus, hma mice constitute a suitable model to further dissect the
interactions between pathogens, human microbiota and vertebrate host immunity
during acute intestinal inflammation