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Bone marrow dendritic cells from mice with an altered microbiota provide interleukin 17A-dependent protection against Entamoeba histolytica colitis.

Burgess SL, Buonomo E, Carey M, Cowardin C, Naylor C, Noor Z, Wills-Karp M, Petri WA - MBio (2014)

Bottom Line: SFB colonization in this model was associated with elevated cecal levels of interleukin 17A (IL-17A), dendritic cells, and neutrophils.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA.

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BMDCS from SFB-colonized mice migrated to the lamina propria of SFB-free mice upon adoptive transfer via the intraperitoneal route. Bone marrow cells (500,000) from SFB+ or SFB− mice were CFSE stained and adoptively transferred to 5-week-old CBA/J mice free of SFB. Flow cytometry for CFSE staining was performed on single cells isolated from spleens, Peyer’s patches (PP), mesenteric lymph nodes (MLN), and lamina propria (LP). *, P < 0.05.
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fig4: BMDCS from SFB-colonized mice migrated to the lamina propria of SFB-free mice upon adoptive transfer via the intraperitoneal route. Bone marrow cells (500,000) from SFB+ or SFB− mice were CFSE stained and adoptively transferred to 5-week-old CBA/J mice free of SFB. Flow cytometry for CFSE staining was performed on single cells isolated from spleens, Peyer’s patches (PP), mesenteric lymph nodes (MLN), and lamina propria (LP). *, P < 0.05.

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).


Bone marrow dendritic cells from mice with an altered microbiota provide interleukin 17A-dependent protection against Entamoeba histolytica colitis.

Burgess SL, Buonomo E, Carey M, Cowardin C, Naylor C, Noor Z, Wills-Karp M, Petri WA - MBio (2014)

BMDCS from SFB-colonized mice migrated to the lamina propria of SFB-free mice upon adoptive transfer via the intraperitoneal route. Bone marrow cells (500,000) from SFB+ or SFB− mice were CFSE stained and adoptively transferred to 5-week-old CBA/J mice free of SFB. Flow cytometry for CFSE staining was performed on single cells isolated from spleens, Peyer’s patches (PP), mesenteric lymph nodes (MLN), and lamina propria (LP). *, P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4222101&req=5

fig4: BMDCS from SFB-colonized mice migrated to the lamina propria of SFB-free mice upon adoptive transfer via the intraperitoneal route. Bone marrow cells (500,000) from SFB+ or SFB− mice were CFSE stained and adoptively transferred to 5-week-old CBA/J mice free of SFB. Flow cytometry for CFSE staining was performed on single cells isolated from spleens, Peyer’s patches (PP), mesenteric lymph nodes (MLN), and lamina propria (LP). *, P < 0.05.
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).

Bottom Line: SFB colonization in this model was associated with elevated cecal levels of interleukin 17A (IL-17A), dendritic cells, and neutrophils.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA.

Show MeSH
Related in: MedlinePlus