Malaria oocysts require circumsporozoite protein to evade mosquito immunity.
Malaria oocysts require circumsporozoite protein to evade mosquito immunity.
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DOI：
10.1038/s41467-022-30988-z
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发表时间：
2022-06-09
影响因子：
16.6
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中科院分区：
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一旦动合子转化为卵囊，疟原虫就不那么容易受到蚊子免疫应答的影响，从而促进蚊子中的寄生虫发育。然而，卵囊抵抗蚊子防御的潜在机制仍不清楚。在这里，我们表明，环子孢子蛋白（CSP）所需的啮齿动物疟疾卵囊，以避免蚊子的防御。CSPmut寄生虫（CSP pexel I/II结构域中的突变）的Moscovirus感染诱导烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶5（NOX 5）介导的血细胞硝化，从而激活Toll途径和成熟卵囊的黑化，上调血细胞TEP 1表达，并导致子孢子从卵囊释放的缺陷。用CSPmut寄生虫预感染蚊子通过诱导血细胞硝化降低了用CSPwt寄生虫再次攻击时的感染负担。因此，我们证明了为什么卵囊对蚊子免疫是不可见的，并揭示了CSP在卵囊免疫逃避中的未知作用，表明它是阻断疟疾传播的潜在靶点。疟原虫环子孢子蛋白（Circumsporozoite protein，CSP）是疟原虫子孢子的主要表面蛋白，在疟原虫以蚊子唾液腺和哺乳动物肝脏为靶标的过程中起着重要作用。在这里，Zhu等人表明CSP是啮齿类疟疾卵囊通过诱导血细胞硝化和导致随后的子孢子从卵囊释放缺陷来逃避蚊子免疫所必需的。
Malaria parasites are less vulnerable to mosquito immune responses once ookinetes transform into oocysts, facilitating parasite development in the mosquito. However, the underlying mechanisms of oocyst resistance to mosquito defenses remain unclear. Here, we show that circumsporozoite protein (CSP) is required for rodent malaria oocysts to avoid mosquito defenses. Mosquito infection with CSPmut parasites (mutation in the CSP pexel I/II domains) induces nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 5 (NOX5)-mediated hemocyte nitration, thus activating Toll pathway and melanization of mature oocysts, upregulating hemocyte TEP1 expression, and causing defects in the release of sporozoites from oocysts. The pre-infection of mosquitoes with the CSPmut parasites reduces the burden of infection when re-challenged with CSPwt parasites by inducing hemocyte nitration. Thus, we demonstrate why oocysts are invisible to mosquito immunity and reveal an unknown role of CSP in the immune evasion of oocysts, indicating it as a potential target to block malaria transmission. Circumsporozoite protein (CSP), the major surface protein of Plasmodium sporozoites, is important for parasite targeting to mosquito salivary glands and the mammalian liver. Here, Zhu et al. show that CSP is required for rodent malaria oocysts to evade mosquito immunity by inducing hemocyte nitration and causing subsequent defects in sporozoite-release from oocysts.
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期刊：
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