Castillo Julio César, Ferreira Ana Beatriz Barletta, Trisnadi Nathanie, Barillas-Mury Carolina
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20892, USA.
Sci Immunol. 2017 Jan;2(7). doi: 10.1126/sciimmunol.aal1505. Epub 2017 Jan 20.
The mosquito complement-like system is a major defense mechanism that limits infection. Ookinete midgut invasion results in irreversible damage to invaded cells and triggers epithelial nitration and complement activation. Several lines of evidence suggest that hemocytes participate in early antiplasmodial responses that target ookinetes, but their role remains unclear. The fate of hemocytes in response to infection was investigated by labeling this cell population in vivo. We found that midgut nitration triggers the local release of hemocyte-derived microvesicles (HdMv) into the basal labyrinth of the midgut. Several different strategies, such as gene silencing, immune priming, or systemic injection of polystyrene beads, were used to either enhance or reduce HdMv release. We provide direct experimental evidence that contact of hemocytes with the nitrated midgut basal surface triggers HdMv release and that this response is necessary for effective activation of mosquito complement. Our studies suggest that hemocyte-derived microvesicles may deliver some critical factor(s) that promote activation of thioester-containing protein 1, a key effector of the mosquito antiplasmodial immunity.
蚊子的补体样系统是限制感染的主要防御机制。动合子对中肠的入侵会对被入侵细胞造成不可逆的损伤，并引发上皮细胞硝化作用和补体激活。多项证据表明，血细胞参与针对动合子的早期抗疟原虫反应，但其作用仍不明确。通过在体内标记血细胞群体，研究了血细胞在感染后的命运。我们发现中肠硝化作用会触发血细胞衍生的微囊泡（HdMv）局部释放到中肠的基底迷路中。我们采用了几种不同的策略，如基因沉默、免疫致敏或全身注射聚苯乙烯珠粒，来增强或减少HdMv的释放。我们提供了直接的实验证据，即血细胞与硝化的中肠基底表面接触会触发HdMv释放，并且这种反应对于有效激活蚊子补体是必要的。我们的研究表明，血细胞衍生的微囊泡可能会传递一些关键因子，这些因子可促进含硫酯蛋白1的激活，含硫酯蛋白1是蚊子抗疟原虫免疫的关键效应因子。
