Ou Jiayao, Liang Shaonan, Guo Xue-Kun, Hu Xiaoyu
Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China.
Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China.
Front Immunol. 2020 Sep 9;11:2065. doi: 10.3389/fimmu.2020.02065. eCollection 2020.
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 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 from the mucosal reservoir following antibiotics-induced dysbiosis, shown by markedly compromised recovery of in animals. Mechanistically, α-defensins promote colonization on epithelial surfaces and adhesion to epithelial cells . Moreover, α-defensins unexpectedly does not show any microbicidal activities against . Together, we propose that α-defensins promote commensal bacterial colonization and recovery to maintain microbial diversity upon environmental challenges.
除了在宿主防御中已确立的功能外，越来越多的证据表明抗菌蛋白（AMPs）在塑造共生微生物群方面发挥着新的作用。然而，α-防御素作为肠道中最丰富的AMPs，在调节微生物生态方面的作用仍无定论。在此，我们报告α-防御素通过增强细菌对黏膜储存库的黏附来促进共生菌的定殖。利用基质金属蛋白酶7（MMP7）缺陷小鼠（α-防御素激活酶）并设置严格的同窝对照进行实验，结果表明α-防御素缺陷对稳态肠道微生物群没有显著影响。相反，抗生素诱导的生态失调后，α-防御素对于从黏膜储存库补充共生菌至关重要，这在α-防御素缺陷动物中明显受损的恢复情况中得到体现。从机制上讲，α-防御素促进共生菌在上皮表面的定殖以及对上皮细胞的黏附。此外，α-防御素出人意料地对共生菌没有任何杀菌活性。我们共同提出，α-防御素促进共生菌的定殖和恢复，以在环境挑战时维持微生物多样性。
