PGRP-LD mediates A. stephensi vector competency by regulating homeostasis of microbiota-induced peritrophic matrix synthesis.

PGRP-LD mediates A. stephensi vector competency by regulating homeostasis of microbiota-induced peritrophic matrix synthesis.
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PGRP-LD 通过调节微生物群诱导的围营养基质合成的稳态来介导 A.stephensi 载体能力

DOI:
10.1371/journal.ppat.1006899
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发表时间:
2018-03
期刊:
影响因子:
6.7
通讯作者:
Wang J
Wang J
中科院分区:
医学1区
文献类型:
--
作者:
Song X;Wang M;Dong L;Zhu H;Wang J

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肽聚糖识别蛋白(PGRP)和昆虫病原微生物介导昆虫疾病媒介中的病原体感染结果。尽管PGRP-LD保留在多种载体中,但其在宿主防御中的作用仍然难以捉摸。在这里,我们报告说,斯氏按蚊PGRP-LD保护疟疾寄生虫感染的载体,通过调节肠道内稳态。具体而言,PGRP-LD(dsLD)的敲低增加了对伯氏疟原虫感染的易感性,降低了肠道微生物群的丰度并改变了它们的空间分布。这一结果是由围食基质(PM)结构完整性的变化引起的,PM是一种排列在中肠腔中的几丁质和蛋白质屏障。由于免疫效应物的上调导致dsLD蚊子中微生物群的减少导致PM基因的失调和PM片段化。抗生素处理的蚊子(Abx)中肠道微生物群的消除导致PM损失和媒介能力增加。Abx蚊子与土著肠杆菌属的重新定殖恢复PM的完整性和降低蚊子的媒介能力。在无PM的蚊子中沉默PGRP-LD不影响其媒介能力。我们的研究结果表明,PGPR-LD通过防止超免疫来保护肠道微生物群,这反过来又促进PM结构的完整性。完整的PM在限制伯氏疟原虫感染中起关键作用。
Peptidoglycan recognition proteins (PGRPs) and commensal microbes mediate pathogen infection outcomes in insect disease vectors. Although PGRP-LD is retained in multiple vectors, its role in host defense remains elusive. Here we report that Anopheles stephensi PGRP-LD protects the vector from malaria parasite infection by regulating gut homeostasis. Specifically, knock down of PGRP-LD (dsLD) increased susceptibility to Plasmodium berghei infection, decreased the abundance of gut microbiota and changed their spatial distribution. This outcome resulted from a change in the structural integrity of the peritrophic matrix (PM), which is a chitinous and proteinaceous barrier that lines the midgut lumen. Reduction of microbiota in dsLD mosquitoes due to the upregulation of immune effectors led to dysregulation of PM genes and PM fragmentation. Elimination of gut microbiota in antibiotic treated mosquitoes (Abx) led to PM loss and increased vectorial competence. Recolonization of Abx mosquitoes with indigenous Enterobacter sp. restored PM integrity and decreased mosquito vectorial capacity. Silencing PGRP-LD in mosquitoes without PM didn’t influence their vector competence. Our results indicate that PGPR-LD protects the gut microbiota by preventing hyper-immunity, which in turn promotes PM structurally integrity. The intact PM plays a key role in limiting P. berghei infection.
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