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

TitleGut Microbial Dysbiosis Due to Helicobacter Drives an Increase in Marginal Zone B Cells in the Absence of IL-10 Signaling in Macrophages.
Publication TypeJournal Article
Year of Publication2015
AuthorsRay 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
JournalJ Immunol
Volume195
Issue7
Pagination3071-85
Date Published2015 Oct 01
ISSN1550-6606
KeywordsAnimals, Base Sequence, B-Lymphocytes, Cell Count, Cell Differentiation, Cell Proliferation, DNA, Bacterial, Dysbiosis, Enterocolitis, Gastrointestinal Microbiome, Helicobacter hepaticus, Helicobacter Infections, Interleukin-10, Lymphocyte Activation, Lymphoid Tissue, Macrophages, Mice, Mice, Inbred C57BL, Mice, Knockout, Neutrophils, RNA, Ribosomal, 16S, Sequence Analysis, DNA, Signal Transduction
Abstract

<p>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.</p>

DOI10.4049/jimmunol.1500153
Alternate JournalJ. Immunol.
PubMed ID26324769
PubMed Central IDPMC4575870
Grant ListP30 AI027767 / AI / NIAID NIH HHS / United States
R56 AI106672 / AI / NIAID NIH HHS / United States
R01 DK088831 / DK / NIDDK NIH HHS / United States
UL1TR000165 / TR / NCATS NIH HHS / United States
P30AR050948 / AR / NIAMS NIH HHS / United States
UL1 TR000165 / TR / NCATS NIH HHS / United States
P30 CA013148 / CA / NCI NIH HHS / United States
R01 AI056153 / AI / NIAID NIH HHS / United States
R56 AI106672-01 / AI / NIAID NIH HHS / United States
R01 AI069358-01A2 / AI / NIAID NIH HHS / United States
P30 AR050948 / AR / NIAMS NIH HHS / United States
R01 GM099526 / GM / NIGMS NIH HHS / United States
UL1 TR001417 / TR / NCATS NIH HHS / United States
R01 AI069358 / AI / NIAID NIH HHS / United States
R21 AI097619 / AI / NIAID NIH HHS / United States
U42 OD010918 / OD / NIH HHS / United States