α-Defensins Promote Bacteroides Colonization on Mucosal Reservoir to Prevent Antibiotic-Induced Dysbiosis

In addition to their established functions in host defense, accumulating evidence has suggested an emerging role for antimicrobial proteins (AMPs) in shaping commensal microbiota. However, the role of α-defensins, the most abundant AMPs of intestine, in regulating microbial ecology remains inconclus...

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Main Authors: Jiayao Ou, Shaonan Liang, Xue-Kun Guo, Xiaoyu Hu
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-09-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2020.02065/full
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author Jiayao Ou
Jiayao Ou
Jiayao Ou
Shaonan Liang
Shaonan Liang
Shaonan Liang
Xue-Kun Guo
Xue-Kun Guo
Xue-Kun Guo
Xiaoyu Hu
Xiaoyu Hu
Xiaoyu Hu
author_facet Jiayao Ou
Jiayao Ou
Jiayao Ou
Shaonan Liang
Shaonan Liang
Shaonan Liang
Xue-Kun Guo
Xue-Kun Guo
Xue-Kun Guo
Xiaoyu Hu
Xiaoyu Hu
Xiaoyu Hu
author_sort Jiayao Ou
collection DOAJ
description In addition to their established functions in host defense, accumulating evidence has suggested an emerging role for antimicrobial proteins (AMPs) in shaping commensal microbiota. However, the role of α-defensins, the most abundant AMPs of intestine, in regulating microbial ecology remains inconclusive. Here, we report that α-defensins promote commensal Bacteroides colonization by enhancing bacterial adhesion to the mucosal reservoir. Experiments utilizing mice deficient in matrix metalloproteinase 7 (MMP7), the α-defensin–activating enzyme, with rigorous littermate controls showed that α-defensin deficiency did not significantly influence steady-state intestinal microbiota. In contrast, α-defensins are essential for replenishment of commensal Bacteroides from the mucosal reservoir following antibiotics-induced dysbiosis, shown by markedly compromised recovery of Bacteroides in Mmp7−/− animals. Mechanistically, α-defensins promote Bacteroides colonization on epithelial surfaces in vivo and adhesion to epithelial cells in vitro. Moreover, α-defensins unexpectedly does not show any microbicidal activities against Bacteroides. Together, we propose that α-defensins promote commensal bacterial colonization and recovery to maintain microbial diversity upon environmental challenges.
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spelling doaj.art-5664cbd57d7f4de58c4860990f13204e2022-12-21T23:47:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-09-011110.3389/fimmu.2020.02065553370α-Defensins Promote Bacteroides Colonization on Mucosal Reservoir to Prevent Antibiotic-Induced DysbiosisJiayao Ou0Jiayao Ou1Jiayao Ou2Shaonan Liang3Shaonan Liang4Shaonan Liang5Xue-Kun Guo6Xue-Kun Guo7Xue-Kun Guo8Xiaoyu Hu9Xiaoyu Hu10Xiaoyu Hu11Institute for Immunology and School of Medicine, Tsinghua University, Beijing, ChinaTsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, ChinaBeijing Key Laboratory for Immunological Research on Chronic Diseases, Tsinghua University, Beijing, ChinaInstitute for Immunology and School of Medicine, Tsinghua University, Beijing, ChinaTsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, ChinaBeijing Key Laboratory for Immunological Research on Chronic Diseases, Tsinghua University, Beijing, ChinaInstitute for Immunology and School of Medicine, Tsinghua University, Beijing, ChinaTsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, ChinaBeijing Key Laboratory for Immunological Research on Chronic Diseases, Tsinghua University, Beijing, ChinaInstitute for Immunology and School of Medicine, Tsinghua University, Beijing, ChinaTsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, ChinaBeijing Key Laboratory for Immunological Research on Chronic Diseases, Tsinghua University, Beijing, ChinaIn addition to their established functions in host defense, accumulating evidence has suggested an emerging role for antimicrobial proteins (AMPs) in shaping commensal microbiota. However, the role of α-defensins, the most abundant AMPs of intestine, in regulating microbial ecology remains inconclusive. Here, we report that α-defensins promote commensal Bacteroides colonization by enhancing bacterial adhesion to the mucosal reservoir. Experiments utilizing mice deficient in matrix metalloproteinase 7 (MMP7), the α-defensin–activating enzyme, with rigorous littermate controls showed that α-defensin deficiency did not significantly influence steady-state intestinal microbiota. In contrast, α-defensins are essential for replenishment of commensal Bacteroides from the mucosal reservoir following antibiotics-induced dysbiosis, shown by markedly compromised recovery of Bacteroides in Mmp7−/− animals. Mechanistically, α-defensins promote Bacteroides colonization on epithelial surfaces in vivo and adhesion to epithelial cells in vitro. Moreover, α-defensins unexpectedly does not show any microbicidal activities against Bacteroides. Together, we propose that α-defensins promote commensal bacterial colonization and recovery to maintain microbial diversity upon environmental challenges.https://www.frontiersin.org/article/10.3389/fimmu.2020.02065/fullantimicrobial proteinsα-defensinsmicrobiota colonizationmucosal reservoirintestinal epithelial cell
spellingShingle Jiayao Ou
Jiayao Ou
Jiayao Ou
Shaonan Liang
Shaonan Liang
Shaonan Liang
Xue-Kun Guo
Xue-Kun Guo
Xue-Kun Guo
Xiaoyu Hu
Xiaoyu Hu
Xiaoyu Hu
α-Defensins Promote Bacteroides Colonization on Mucosal Reservoir to Prevent Antibiotic-Induced Dysbiosis
Frontiers in Immunology
antimicrobial proteins
α-defensins
microbiota colonization
mucosal reservoir
intestinal epithelial cell
title α-Defensins Promote Bacteroides Colonization on Mucosal Reservoir to Prevent Antibiotic-Induced Dysbiosis
title_full α-Defensins Promote Bacteroides Colonization on Mucosal Reservoir to Prevent Antibiotic-Induced Dysbiosis
title_fullStr α-Defensins Promote Bacteroides Colonization on Mucosal Reservoir to Prevent Antibiotic-Induced Dysbiosis
title_full_unstemmed α-Defensins Promote Bacteroides Colonization on Mucosal Reservoir to Prevent Antibiotic-Induced Dysbiosis
title_short α-Defensins Promote Bacteroides Colonization on Mucosal Reservoir to Prevent Antibiotic-Induced Dysbiosis
title_sort α defensins promote bacteroides colonization on mucosal reservoir to prevent antibiotic induced dysbiosis
topic antimicrobial proteins
α-defensins
microbiota colonization
mucosal reservoir
intestinal epithelial cell
url https://www.frontiersin.org/article/10.3389/fimmu.2020.02065/full
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