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J Immunol. 2015 Oct 1;195(7):3071-85. doi: 10.4049/jimmunol.1500153. Epub 2015 Aug 31.

Gut Microbial Dysbiosis Due to Helicobacter Drives an Increase in Marginal Zone B Cells in the Absence of IL-10 Signaling in Macrophages.

Author information

1
Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53201;
2
Bioinformatics Services Division, Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC 28223; Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC 28223;
3
Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211;
4
Center for Clinical and Translational Sciences, University of Alabama at Birmingham, Birmingham, AL 35233;
5
Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham AL 35233;
6
Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, United Kingdom;
7
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35233;
8
Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105; and.
9
Division of Gastroenterology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226.
10
Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC 28223;
11
Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53201; bonnie.dittel@bcw.edu.

Abstract

It is clear that IL-10 plays an essential role in maintaining homeostasis in the gut in response to the microbiome. However, it is unknown whether IL-10 also facilitates immune homeostasis at distal sites. To address this question, we asked whether splenic immune populations were altered in IL-10-deficient (Il10(-/-)) mice in which differences in animal husbandry history were associated with susceptibility to spontaneous enterocolitis that is microbiome dependent. The susceptible mice exhibited a significant increase in splenic macrophages, neutrophils, and marginal zone (MZ) B cells that was inhibited by IL-10 signaling in myeloid, but not B cells. The increase in macrophages was due to increased proliferation that correlated with a subsequent enhancement in MZ B cell differentiation. Cohousing and antibiotic treatment studies suggested that the alteration in immune homeostasis in the spleen was microbiome dependent. The 16S rRNA sequencing revealed that susceptible mice harbored a different microbiome with a significant increase in the abundance of the bacterial genus Helicobacter. The introduction of Helicobacter hepaticus to the gut of nonsusceptible mice was sufficient to drive macrophage expansion and MZ B cell development. Given that myeloid cells and MZ B cells are part of the first line of defense against blood-borne pathogens, their increase following a breach in the gut epithelial barrier would be protective. Thus, IL-10 is an essential gatekeeper that maintains immune homeostasis at distal sites that can become functionally imbalanced upon the introduction of specific pathogenic bacteria to the intestinal track.

PMID:
26324769
PMCID:
PMC4575870
DOI:
10.4049/jimmunol.1500153
[Indexed for MEDLINE]
Free PMC Article

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