Title |
Gut Microbial Dysbiosis Due to Helicobacter Drives an Increase in Marginal Zone B Cells in the Absence of IL-10 Signaling in Macrophages
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Published in |
The Journal of Immunology, October 2015
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DOI | 10.4049/jimmunol.1500153 |
Pubmed ID | |
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 |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 1 | 50% |
Unknown | 1 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Canada | 2 | 4% |
Unknown | 44 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 7 | 15% |
Student > Bachelor | 6 | 13% |
Professor | 5 | 11% |
Student > Doctoral Student | 4 | 9% |
Student > Ph. D. Student | 4 | 9% |
Other | 8 | 17% |
Unknown | 12 | 26% |
Readers by discipline | Count | As % |
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Agricultural and Biological Sciences | 8 | 17% |
Immunology and Microbiology | 7 | 15% |
Medicine and Dentistry | 6 | 13% |
Biochemistry, Genetics and Molecular Biology | 3 | 7% |
Veterinary Science and Veterinary Medicine | 3 | 7% |
Other | 4 | 9% |
Unknown | 15 | 33% |