BACKGROUND Malaria remains to be one of the deadliest infectious diseases and imposes substantial financial and social costs in the world. Mosquitoes rely on the immune system to control parasite infection. Peptidoglycan recognition proteins (PGRPs), a family of pattern-recognition receptors (PRR), are responsible for initiating and regulating immune signaling pathways. PGRP-LA is involved in the regulation of immune defense against the Plasmodium parasite, however, the underlying mechanism needs to be further elucidated. METHODS The spatial and temporal expression patterns of pgrp-la in Anopheles stephensi were analyzed by qPCR. The function of PGRP-LA was examined using a dsRNA-based RNA interference strategy. Western blot and periodic acid schiff (PAS) staining were used to assess the structural integrity of peritrophic matrix (PM). RESULTS The expression of pgrp-la in An. stephensi was induced in the midgut in response to the rapid proliferating gut microbiota post-blood meal. Knocking down of pgrp-la led to the downregulation of immune effectors that control gut microbiota growth. The decreased expression of these immune genes also facilitated P. berghei infection. However, such dsLA treatment did not influence the structural integrity of PM. When gut microbiota was removed by antibiotic treatment, the regulation of PGRP-LA on immune effectors was abolished and the knock down of pgrp-la failed to increase susceptibility of mosquitoes to parasite infection. CONCLUSIONS PGRP-LA regulates the immune responses by sensing the dynamics of gut microbiota. A mutual interaction between gut microbiota and PGRP-LA contributes to the immune defense against Plasmodium parasites in An. stephensi.

中文翻译：

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肠道菌群对于PGRP-LA调节的针对伯氏疟原虫感染的免疫保护至关重要。

背景技术疟疾仍然是最致命的传染病之一，并且在世界上造成巨大的经济和社会成本。蚊子依靠免疫系统控制寄生虫感染。肽聚糖识别蛋白（PGRPs）是模式识别受体（PRR）的一个家族，负责启动和调节免疫信号通路。PGRP-LA参与了针对疟原虫寄生虫的免疫防御的调控，但是，其潜在机制有待进一步阐明。方法采用qPCR方法分析斯蒂芬按蚊中pgrp-la的时空表达模式。使用基于dsRNA的RNA干扰策略检查了PGRP-LA的功能。Western blot和高碘酸席夫（PAS）染色用于评估周围营养基质（PM）的结构完整性。结果pgrp-1a在An中的表达。食后快速繁殖的肠道菌群在中肠诱发了斯蒂芬斯。敲低pgrp-la导致控制肠道菌群生长的免疫效应子下调。这些免疫基因表达的降低也促进了伯氏疟原虫感染。但是，这种dsLA处理不会影响PM的结构完整性。当通过抗生素治疗去除肠道菌群时，PGRP-LA对免疫效应子的调节被取消，而敲除pgrp-la并不能增加蚊子对寄生虫感染的敏感性。结论PGRP-LA通过感知肠道菌群的动态来调节免疫反应。肠道菌群与PGRP-LA之间的相互作用有助于对An。疟原虫的免疫防御。