Bone Marrow Dendritic Cells from Mice with an Altered Microbiota Provide Interleukin 17A-Dependent Protection against Entamoeba histolytica Colitis

Burgess, Stacey L.; Buonomo, Erica; Carey, Maureen; Cowardin, Carrie; Naylor, Caitlin; Noor, Zannatun; Wills-Karp, Marsha; Petri, William A.

There is an emerging paradigm that the human microbiome is central to many aspects of health and may have a role in preventing enteric infection. Entamoeba histolytica is a major cause of amebic diarrhea in developing countries. It colonizes the colon lumen in close proximity to the gut microbiota. Interestingly, not all individuals are equally susceptible to E. histolytica infection. Therefore, as the microbiota is highly variable within individuals, we sought to determine if a component of the microbiota could regulate susceptibility to infection. In studies utilizing a murine model, we demonstrated that colonization of the gut with the commensal Clostridia-related bacteria known as segmented filamentous bacteria (SFB) is protective during E. histolytica infection. SFB colonization in this model was associated with elevated cecal levels of interleukin 17A (IL-17A), dendritic cells, and neutrophils. Bone marrow-derived dendritic cells (BMDCs) from SFB-colonized mice had higher levels of IL-23 production in response to stimulation with trophozoites. Adoptive transfer of BMDCs from an SFB(+) to an SFB(−) mouse was sufficient to provide protection against E. histolytica. IL-17A induction during BMDC transfer was necessary for this protection. This work demonstrates that intestinal colonization with a specific commensal bacterium can provide protection during amebiasis in a murine model. Most importantly, this work demonstrates that the microbiome can mediate protection against an enteric infection via extraintestinal effects on bone marrow-derived dendritic cells.