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

Authors:
Avijit Ray, PhD
Avijit Ray, PhD
AbbVie
Senior Scientist II
Immunology, Immuno-oncology, Autoimmunity and Inflammation, Immune tolerance
North Chicago, IL | United States
Sreemanti Basu
Sreemanti Basu
Blood Research Institute
United States
Raad Z Gharaibeh
Raad Z Gharaibeh
University of North Carolina at Charlotte
United States
Ranjit Kumar
Ranjit Kumar
Center for Clinical and Translational Sciences
Sacramento | United States
Elliot J Lefkowitz
Elliot J Lefkowitz
Center for Clinical and Translational Sciences
Sacramento | United States
Catherine R Walker
Catherine R Walker
University of Manchester
United Kingdom
Casey D Morrow
Casey D Morrow
University of Alabama at Birmingham
United States

J Immunol 2015 Oct 31;195(7):3071-85. Epub 2015 Aug 31.

Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53201;

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.

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Source
http://dx.doi.org/10.4049/jimmunol.1500153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4575870PMC

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October 2015
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