Bone marrow dendritic cells from mice with an altered microbiota provide interleukin 17A-dependent protection against Entamoeba histolytica colitis.
Bottom Line: Most importantly, this work demonstrates that the microbiome can mediate protection against an enteric infection via extraintestinal effects on bone marrow-derived dendritic cells.Entamoeba histolytica is the causative agent of amebiasis, an infectious disease that contributes significantly to morbidity and mortality due to diarrhea in the developing world.The demonstration of immune-mediated protection due to communication from the microbiome to the bone marrow represents an emerging field of study that will yield unique approaches to the development of these treatments.
Affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA.Show MeSH
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Mentions: As cohousing of mice both transferred SFB and was protective against E. histolytica infection, we sought to determine if SFB specifically provided protection against the ameba. We directly colonized CBA/J mice from Jackson Laboratories with SFB by orogastric gavage with SFB-monoassociated feces resuspended in phosphate-buffered saline (PBS), provided by the Yakult Central Institute for Microbiological Studies, 1 week prior to E. histolytica infection. Mice became colonized with SFB following gavage (Fig. 2A) and were protected from infection with the ameba (Fig. 2B). Additionally, there was increased IL-17A and IL-23 expression before (Fig. S1) and after (Fig. 2C and D) E. histolytica infection. Neutrophils (Fig. 2E; also, see Fig. S1c in the supplemental material) and DCs (Fig. 2F; also, see Fig. S1d in the supplemental material) were also elevated in the intestine of SFB colonized mice after E. histolytica infection. We also observed increased SAA in serum in SFB-colonized mice after ameba infection (Fig. 2G).
Affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA.