Qin Xin, Li Jianyong, Zhu Feng, Zhang Jian
Department of Pathogenic Biology, Army Medical University (Third Military Medical University), Chongqing, 400038, China.
Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, 400038, China.
Parasit Vectors. 2025 Apr 1;18(1):124. doi: 10.1186/s13071-025-06772-5.
Thioester-containing proteins (TEPs) serve as crucial effectors and regulatory components within the innate immune system of mosquitoes. Despite their significance, the mechanisms by which TEPs exert negative regulation on the immune response in mosquitoes remain inadequately understood. This study aims to elucidate the role of TEPs in the negative regulation of melanization, thereby advancing our comprehension of their regulatory function in the immune response.
We infected female Anopheles stephensi mosquitoes with Plasmodium yoelii by allowing them to feed on pre-infected female Kunming mice. Western blot, quantitative polymerase chain reaction, differential gene expression analyses, and gene silencing were then conducted. Student's t-test was used to analyze continuous variables, with statistical significance defined as p < 0.05.
A. stephensi TEP15 (AsTEP15) negatively regulated mosquitos' innate immunity and promoted Plasmodium development. AsTEP15 knockdown induced mosquito resistance to malaria parasite melanization during the oocyst stage and significantly reduced sporozoite numbers. Further analysis showed that AsTEP15 mainly negatively affects the TEP1 and immune deficiency (IMD) pathway, thereby inhibiting melanization.
We describe a mosquito TEP that negatively regulates immunity, further enriching the functional diversity of TEP family members. In addition, our results suggest that oocysts may exploit TEPs to escape or inhibit mosquito immunity, highlighting potential targets for blocking malaria transmission.
含硫酯蛋白（TEPs）是蚊子先天免疫系统中的关键效应分子和调节成分。尽管它们很重要，但TEPs对蚊子免疫反应发挥负调控作用的机制仍未得到充分了解。本研究旨在阐明TEPs在黑化负调控中的作用，从而增进我们对其在免疫反应中调节功能的理解。
我们让雌性斯氏按蚊吸食预先感染了约氏疟原虫的雌性昆明小鼠的血液，从而使这些蚊子感染疟原虫。然后进行蛋白质免疫印迹、定量聚合酶链反应、差异基因表达分析和基因沉默。采用学生t检验分析连续变量，统计学显著性定义为p < 0.05。
斯氏按蚊TEP15（AsTEP15）对蚊子的先天免疫起负调控作用，并促进疟原虫的发育。敲低AsTEP15可诱导蚊子在卵囊阶段对疟原虫黑化产生抗性，并显著减少子孢子数量。进一步分析表明，AsTEP15主要对TEP1和免疫缺陷（IMD）途径产生负面影响，从而抑制黑化。
我们描述了一种对免疫起负调控作用的蚊子TEP，进一步丰富了TEP家族成员的功能多样性。此外，我们的结果表明，卵囊可能利用TEPs来逃避或抑制蚊子的免疫，突出了阻断疟疾传播的潜在靶点。
