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

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.

• Authors: Avijit Ray, Sreemanti Basu, Raad Z Gharaibeh, Lydia C Cook, Ranjit Kumar, Elliot J Lefkowitz, Catherine R Walker, Casey D Morrow, Craig L Franklin, Terrence L Geiger, Nita H Salzman, Anthony Fodor, Bonnie N Dittel
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 195 Issue 7 Pg. 3071-85 (Oct 01 2015) ISSN: 1550-6606 [Electronic] United States
• PMID: 26324769 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 by The American Association of Immunologists, Inc.

Chemical References

• DNA, Bacterial
• IL10 protein, mouse
• RNA, Ribosomal, 16S
• Interleukin-10

Topics

• Animals
• B-Lymphocytes (cytology, immunology)
• Base Sequence
• Cell Count
• Cell Differentiation (immunology)
• Cell Proliferation
• DNA, Bacterial (genetics)
• Dysbiosis (microbiology)
• Enterocolitis (immunology, microbiology)
• Gastrointestinal Microbiome (genetics)
• Helicobacter Infections (immunology, microbiology)
• Helicobacter hepaticus (immunology)
• Interleukin-10 (genetics, immunology)
• Lymphocyte Activation (immunology)
• Lymphoid Tissue (cytology, immunology)
• Macrophages (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Neutrophils (immunology)
• RNA, Ribosomal, 16S (genetics)
• Sequence Analysis, DNA
• Signal Transduction (immunology)