Faculty Collaboration Database

Gut Microbial Dysbiosis Due to Helicobacter Drives an Increase in Marginal Zone B Cells in the Absence of IL-10 Signaling in Macrophages. J Immunol 2015 Oct 01;195(7):3071-85

Date

09/02/2015

Pubmed ID

26324769

Pubmed Central ID

PMC4575870

DOI

10.4049/jimmunol.1500153

Scopus ID

2-s2.0-84942475191 (requires institutional sign-in at Scopus site)   23 Citations

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.

Author List

Ray A, Basu S, Gharaibeh RZ, Cook LC, Kumar R, Lefkowitz EJ, Walker CR, Morrow CD, Franklin CL, Geiger TL, Salzman NH, Fodor A, Dittel BN

Author

Nita H. Salzman PhD, MD Center Director, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

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