Defining cooperative roles for colonic microbiota and Muc2 mucin in mediating innate host defense against Entamoeba histolytica.

摘要: Amebiasis is caused by the protozoan parasite Entamoeba histolytica (Eh), a potentially fatal disease occurring mainly in developing countries. How Eh interacts with innate host factors gut poorly understood. resides and feed in/on outer colonic mucus layer thus share an ecological niche indigenous microbiota. As microbiota regulates immune responses, this study we characterized cooperative roles that play Eh-induced pro-inflammatory responses colon. To this, used antibiotics treated non-treated specific pathogen free Muc2-/- Muc2+/+ littermates germ-free mice inoculated loops as short infection model. In antibiotic littermates, elicited robust water secretions, enhanced cytokines chemokine expression elevated MPO activity higher pathology scores compared to modest response observed non-antibiotic littermates. Host were secretion attenuated following homologous fecal microbial transplants antibiotic-treated quantified of 3H-glucosamine newly synthesized mucin, Muc2 mucin immunostaining immunohistochemistry. Eh-elicited suppressed goblet cell transcription factor Math1 revealed vivo imaging Eh-colonic Math1GFP mice, vitro using Eh-stimulated LS174T human cells. increased bacterial translocation bioluminescent E. coli bacteria FISH quantitative PCR. animals, mucus/water secretory but acute severely impaired, allowing bind disrupt mucosal epithelial These findings have identified key for intestinal regulating defenses against Eh, implicate dysbiosis risk amebiasis leads exacerbated cause life-threatening disease.