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.

肽聚糖识别蛋白（PGRP）和共生微生物介导昆虫疾病载体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，我们报告说按蚊PGRP-LD通过调节肠道稳态来保护载体免受疟原虫感染。具体而言，敲低PGRP-LD（dsLD）会增加对伯氏疟原虫的敏感性感染，减少了肠道菌群的丰度并改变了它们的空间分布。这一结果是由于营养周质基质（PM）的结构完整性发生变化而引起的，营养周质基质（PM）是覆盖中肠腔的几丁质和蛋白质屏障。dsLD蚊子中微生物群的减少（由于免疫效应子的上调引起）导致PM基因失调和PM片段化。消除经抗生素处理的蚊子（Abx）中的肠道菌群可导致PM丢失和矢量能力增强。用本地肠杆菌重新定殖Abx蚊子。恢复了PM完整性并降低了蚊虫的媒介能力。使没有PM的蚊子沉默PGRP-LD不会影响它们的媒介能力。我们的结果表明，PGPR-LD通过防止过度免疫来保护肠道菌群，进而促进PM结构完整性。完整的PM在限制P中起关键作用。伯氏感染。