Prostaglandin E2 Signaling Mediates Oenocytoid Immune Cell Function and Lysis, Limiting Bacteria and Plasmodium Oocyst Survival in Anopheles gambiae.
Prostaglandin E2 Signaling Mediates Oenocytoid Immune Cell Function and Lysis, Limiting Bacteria and Plasmodium Oocyst Survival in Anopheles gambiae.
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DOI：
10.3389/fimmu.2021.680020
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发表时间：
2021
影响因子：
7.3
通讯作者：
Smith RC
中科院分区：
文献类型：
--
作者：
Kwon H;Hall DR;Smith RC
被称为类二十烷酸的脂质衍生的信号分子在介导多细胞动物的免疫和炎症过程中具有不可或缺的作用。这包括白藜芦醇及其同源G蛋白偶联受体（GPCR）发挥其免疫作用的功能。在昆虫中，野牡丹素涉及细胞和体液免疫应答的调节，但在具有医学重要性的节肢动物中，研究有限。在这里，我们描述了一个前列腺素E2受体（AgPGE2R）在蚊子冈比亚按蚊，并证明其表达是最丰富的oenocytoid免疫细胞群体。通过管理的前列腺素E2（PGE2）和AgPGE2R沉默，我们证明，前列腺素E2信号调节一个子集的酚氧化酶（PPOS）和抗菌肽（AMP），强烈表达的群体oenocytoids。我们证明，PGE2信号通过AgPGE2R显着限制细菌复制和疟原虫卵囊存活。另外的实验证实，PGE2处理通过增加PPO1和PPO3的表达来增加酚氧化酶（PO）活性，PPO1和PPO3是促进卵囊杀死的抗疟原虫免疫应答所必需的基因。我们还提供了证据表明，PGE2信号传导的机制是浓度依赖性的，其中高浓度的PGE2促进卵母细胞样溶解，否定了低浓度的PGE2对抗疟原虫免疫的保护作用。总之，我们的研究结果为PGE2信号对免疫细胞功能的作用及其对促进病原体杀灭的蚊子先天免疫的贡献提供了新的见解。
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 in arthropods of medical importance, studies have been limited. Here, we describe a prostaglandin E2 receptor (AgPGE2R) in the mosquito Anopheles gambiae and demonstrate that its expression is most abundant in oenocytoid immune cell populations. Through the administration of prostaglandin E2 (PGE2) and AgPGE2R-silencing, we demonstrate that prostaglandin E2 signaling regulates a subset of prophenoloxidases (PPOs) and antimicrobial peptides (AMPs) that are strongly expressed in populations of oenocytoids. We demonstrate that PGE2 signaling via the AgPGE2R significantly limits both bacterial replication and Plasmodium oocyst survival. Additional experiments establish that PGE2 treatment increases phenoloxidase (PO) activity through the increased expression of PPO1 and PPO3, genes essential to anti-Plasmodium immune responses that promote oocyst killing. We also provide evidence that the mechanisms of PGE2 signaling are concentration-dependent, where high concentrations of PGE2 promote oenocytoid lysis, negating the protective effects of lower concentrations of PGE2 on anti-Plasmodium immunity. Taken together, our results provide new insights into the role of PGE2 signaling on immune cell function and its contributions to mosquito innate immunity that promote pathogen killing.
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影响因子：
6.7
作者：
Binggeli O;Neyen C;Poidevin M;Lemaitre B
通讯作者：
Lemaitre B
影响因子：
3.8
作者：
Kwon, Hyeogsun;Yang, Yunlong;Pietrantonio, Patricia, V
通讯作者：
Pietrantonio, Patricia, V
影响因子：
5.3
作者：
Hillyer, Julian F.;Strand, Michael R.
通讯作者：
Strand, Michael R.
影响因子：
3
作者：
Kwon, Hyeogsun;Smith, Ryan C.
通讯作者：
Smith, Ryan C.
影响因子：
5.8
作者：
Barletta, Ana Beatriz F.;Trisnadi, Nathanie;Barillas-Mury, Carolina
通讯作者：
Barillas-Mury, Carolina