期刊
JOURNAL OF IMMUNOLOGY
卷 195, 期 7, 页码 3071-3085出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1500153
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资金
- National Institutes of Health [R01 AI069358-01A2, R56 AI106672-01, R21 AI097619, R01 GM099526, R01 DK088831, R01 AI056153]
- Blood-Center Research Foundation
- Microbiome Resource at the University of Alabama at Birmingham: School of Medicine, Comprehensive Cancer Center [P30AR050948]
- Center for AIDS Research [5P30AI027767]
- Center for Clinical Translational Science [UL1TR000165]
- Heflin Center
It is clear that IL-10 plays an essential role inmaintaining homeostasis in the gut in response to themicrobiome. 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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