Microbiota Mediated Protection from Entamoeba histolytica Infection

Previously our laboratory has demonstrated that colonization of the intestine of mice with a commensal Clostridia-related bacterium, segmented filamentous bacteria (SFB), is protective during E. histolytica infection. SFB colonization was associated with increased cecal levels of interleukin 17A (IL-17A), dendritic cells, and neutrophils. Bone marrow-derived dendritic cells (BMDCs) from SFB-colonized mice exhibited higher levels of IL-23 production in response to stimulation with trophozoites and adoptive transfer of those BMDCs provided protection against E. histolytica infection. IL-17A induction during BMDC transfer was necessary for this protection.  This work suggested that alteration of the microbiome may mediate protection against an amoeba infection via extra intestinal effects on bone marrow. In exploring what changes have occurred in the bone marrow of SFB colonized mice we have found increased expression of the GM-CSFR genes CSF2RA and increased expression of the H3K27 demethylase JMJD3 in both whole bone marrow and differentiated BMDCs. Additionally, blockade of GM-CSF during SFB/E.histolytica co-infection abrogated SFB mediated protection. This work suggests that intestinal colonization with SFB may alter bone marrow cells via GM-CSF dependent mechanisms to provide protection from Entamoeba histolytica infection and that these changes might result from long term epigenetic changes to the bone marrow