Lipid-derived signaling molecules known as eicosanoids have integral roles in mediating immune and inflammatory processes across metazoans. This includes the function of prostaglandins and their cognate G protein-coupled receptors (GPCRs) to employ their immunological actions. In insects, prostaglandins have been implicated in the regulation of both cellular and humoral immune responses, yet studies have been limited by the absence of a described prostaglandin receptor. Here, we characterize a prostaglandin E2 receptor (AgPGE2R) in the mosquito Anopheles gambiae and examine its contributions to innate immunity. AgPGE2R expression is most abundant in circulating hemocytes where it is primarily localized to oenocytoid immune cell populations. Through the administration of prostaglandin E2 (PGE2) and AgPGE2R-silencing by RNAi, we demonstrate that PGE2 signaling regulates the expression of a subset of prophenoloxidases (PPOs) and antimicrobial peptides (AMPs). PGE2 priming via the AgPGE2R significantly limited bacterial replication and suppressed Plasmodium oocyst survival. Additional experiments establish that PGE2 priming increases phenoloxidase (PO) activity through the increased expression of PPO1 and PPO3, which significantly influence Plasmodium oocyst survival. We also provide evidence that PGE2 priming is concentration-dependent, where high concentrations of PGE2 promote oenocytoid lysis, negating the protective effects of PGE2 priming on anti-Plasmodium immunity. Taken together, our results characterize the AgPGE2R and the role of prostaglandin signaling on immune cell function, providing new insights into the role of PGE2 on anti-bacterial and anti-Plasmodium immune responses in the mosquito host.

中文翻译：

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鉴定前列腺素E2受体，该受体调节蚊子表皮细胞免疫细胞在限制细菌和寄生虫感染中的功能

来自脂质的信号分子，称为类花生酸，在介导后生动物的免疫和炎症过程中起着不可或缺的作用。这包括前列腺素及其同源G蛋白偶联受体（GPCR）利用其免疫功能的功能。在昆虫中，前列腺素已参与细胞和体液免疫反应的调节，但由于缺少所述前列腺素受体，研究受到了限制。在这里，我们表征了冈比亚按蚊中的前列腺素E2受体（AgPGE2R），并检查了其对先天免疫的作用。AgPGE2R的表达在循环血细胞中最为丰富，主要集中在卵母细胞免疫细胞群体中。通过RNAi对前列腺素E2（PGE2）和AgPGE2R的沉默，我们证明了PGE2信号调节了前酚氧化酶（PPO）和抗菌肽（AMP）的子集的表达。通过AgPGE2R引发的PGE2启动显着限制了细菌复制并抑制了疟原虫卵囊的存活。其他实验确定PGE2引发可通过PPO1和PPO3的表达增加来增加酚氧化酶（PO）的活性，而PPO1和PPO3的表达显着影响疟原虫卵囊的存活。我们还提供证据表明PGE2引发是浓度依赖性的，其中高浓度的PGE2促进卵泡细胞溶解，从而消除了PGE2引发对抗疟原虫免疫的保护作用。两者合计，我们的结果表征了AgPGE2R和前列腺素信号传导在免疫细胞功能中的作用，