Journal Article

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

Moreau, France, Chadee, Kris, Leon-Coria, Aralia, Kumar, Manish

2018

Overview

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

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Amebiasis / Animals / Antibiotics / Bacteria / Biology and Life Sciences / Cell Line / Chemokines / Chronic illnesses / Colon / Colon - metabolism / Colon - pathology / Cytokines / Developing countries / Digestive system / Digestive tract / Dysbacteriosis / E coli / Ecological niches / Entamoeba histolytica / Entamoeba histolytica - immunology / Entamoeba histolytica - metabolism / Entamoeba histolytica - pathogenicity / Epithelial cells / Epithelial Cells - metabolism / Escherichia coli / Fecal microflora / Gastrointestinal Microbiome - immunology / Gastrointestinal tract / Gene expression / Gene Expression Regulation / Germfree / Glucosamine / Goblet cells / Goblet Cells - metabolism / Homology / Humans / Immune response / Immunity, Innate - immunology / Immunohistochemistry / Immunology / Infections / Infectious diseases / Inflammation / Inflammation - pathology / Innate immunity / Intestinal microflora / Intestinal Mucosa - immunology / Intestine / Laboratory rats / LDCs / Legal fees / Math1 protein / Medicine and Health Sciences / Mice / Mice, Inbred C57BL / Microbiota / Microbiota (Symbiotic organisms) / Microorganisms / Mucin / Mucin-1 / Mucin-2 - immunology / Mucins / Mucins - metabolism / Mucosa / Mucus / Niches (Ecology) / Parasites / Parasitic diseases / Pathogenesis / Pathology / Polymerase chain reaction / Protozoa / Risk analysis / Risk factors / Secretions / Specific pathogen free / Studies / Translocation / Transplants / Tropical diseases