Mosquito Midgut Prostaglandin Release Establishes Systemic Immune Priming

Mosquito Midgut Prostaglandin Release Establishes Systemic Immune Priming
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DOI:
10.1016/j.isci.2019.07.012
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发表时间:
2019-09-27
期刊:
影响因子:
5.8
通讯作者:
Barillas-Mury, Carolina
Barillas-Mury, Carolina
中科院分区:
综合性期刊2区
文献类型:
--
作者:
Barletta, Ana Beatriz F.;Trisnadi, Nathanie;Barillas-Mury, Carolina

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感染了疟原虫的冈比亚按蚊对随后的感染产生了更有效的免疫反应。当疟原虫侵入蚊子中肠允许肠道微生物群与上皮细胞接触时,建立启动。该事件之后是血细胞分化因子(HDF)的全身释放,该因子由与Evokin(一种脂质运载蛋白载体)结合的脂氧素A4组成,其增加循环血细胞的比例。我们发现,蚊子中肠细胞产生和释放前列腺素E2(PGE2),吸引血细胞的中肠表面,并提高他们的巡逻活动。全身注射洋地黄素(PGs)重现了引发反应,并通过触发HDF产生增强抗疟原虫免疫力。虽然昆虫缺乏环加氧酶,但两种血红素过氧化物酶HPX7和HPX8催化蚊子中PG生物合成的重要步骤。苔藓虫中肠释放PGE2吸引血细胞并建立对疟原虫感染的持久增强的全身细胞免疫应答。
Anopheles gambiae mosquitoes that have been infected with Plasmodium mount a more effective immune response to a subsequent infection. Priming is established when Plasmodium invasion of the mosquito midgut allows contact of the gut microbiota with epithelial cells. This event is followed by a systemic release of a hemocyte differentiation factor (HDF) consisting of Lipoxin A4 bound to Evokin, a lipocalin carrier, which increases the proportion of circulating hemocytes. We show that mosquito midgut cells produce and release prostaglandin E2 (PGE2), which attracts hemocytes to the midgut surface and enhances their patrolling activity. Systemic injection of prostaglandins (PGs) recapitulates the priming response and enhances antiplasmodial immunity by triggering HDF production. Although insects lack cyclooxygenases, two heme peroxidases, HPX7 and HPX8, catalyze essential steps in PG biosynthesis in mosquitoes. Mosquito midgut PGE2 release attracts hemocytes and establishes a long-lasting enhanced systemic cellular immune response to Plasmodium infection.