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: To test if the increase in DCs in the gut of SFB+ mice was due to a direct effect on the bone marrow, BMDCs from SFB-colonized and SFB-free mice were adoptively transferred to SFB− mice. For in vivo transfers, day 6 BMDC from SFB− and SFB+ mice were matured with LPS (1 µg/ml), and 16 h later, cells were stained with carboxyfluorescein succinimidyl ester (CFSE; 10 nM), and 5 × 105 cells were administered via intraperitoneal injection. CFSE+ BMDC were detected in the lamina propria but only from SFB+ mice (Fig. 4). The ability of SFB+ BMDCs to home to the gut may help explain the increased numbers of DCs seen in the lamina propria of SFB-colonized mice during E. histolytica infection (Fig. 2E). These results were consistent with other studies that have shown that adoptive transfer of LPS-matured BMDCs results in DC trafficking to the intestine (28, 29, 35).
Affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA.