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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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SFB-colonized mice are protected from E. histolytica infection, have increased IL-17A, IL-23, neutrophils, and DCs in their intestines, and have more serum amyloid A (SAA) in their serum. Quantification via qPCR of SFB relative expression compared to total bacteria (A) and enumeration of trophozoites (B) was performed in cecal lysate from mice given gavages with PBS or SFB-monoassociated feces (Yakult) 7 days prior to intracecal infection with E. histolytica. IL-17A (C) and IL-23 (D) induction in ceca (lamina propria) was measured via qPCR, and neutrophil and DC infiltration was measured by flow cytometry and indicated markers (E and F). (G) Serum SAA was measured by ELISA. *, P < 0.05.
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fig2: SFB-colonized mice are protected from E. histolytica infection, have increased IL-17A, IL-23, neutrophils, and DCs in their intestines, and have more serum amyloid A (SAA) in their serum. Quantification via qPCR of SFB relative expression compared to total bacteria (A) and enumeration of trophozoites (B) was performed in cecal lysate from mice given gavages with PBS or SFB-monoassociated feces (Yakult) 7 days prior to intracecal infection with E. histolytica. IL-17A (C) and IL-23 (D) induction in ceca (lamina propria) was measured via qPCR, and neutrophil and DC infiltration was measured by flow cytometry and indicated markers (E and F). (G) Serum SAA was measured by ELISA. *, P < 0.05.

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).


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)

SFB-colonized mice are protected from E. histolytica infection, have increased IL-17A, IL-23, neutrophils, and DCs in their intestines, and have more serum amyloid A (SAA) in their serum. Quantification via qPCR of SFB relative expression compared to total bacteria (A) and enumeration of trophozoites (B) was performed in cecal lysate from mice given gavages with PBS or SFB-monoassociated feces (Yakult) 7 days prior to intracecal infection with E. histolytica. IL-17A (C) and IL-23 (D) induction in ceca (lamina propria) was measured via qPCR, and neutrophil and DC infiltration was measured by flow cytometry and indicated markers (E and F). (G) Serum SAA was measured by ELISA. *, P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: SFB-colonized mice are protected from E. histolytica infection, have increased IL-17A, IL-23, neutrophils, and DCs in their intestines, and have more serum amyloid A (SAA) in their serum. Quantification via qPCR of SFB relative expression compared to total bacteria (A) and enumeration of trophozoites (B) was performed in cecal lysate from mice given gavages with PBS or SFB-monoassociated feces (Yakult) 7 days prior to intracecal infection with E. histolytica. IL-17A (C) and IL-23 (D) induction in ceca (lamina propria) was measured via qPCR, and neutrophil and DC infiltration was measured by flow cytometry and indicated markers (E and F). (G) Serum SAA was measured by ELISA. *, P < 0.05.
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).

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