Department of Biological Sciences, Vanderbilt University, Nashville, TN, USA.
Department of Biological Sciences, Vanderbilt University, Nashville, TN, USA.
Insect Biochem Mol Biol. 2019 Apr;107:1-9. doi: 10.1016/j.ibmb.2019.01.007. Epub 2019 Jan 25.
The mosquito immune and circulatory systems are functionally integrated. During an infection, hemocytes aggregate around the ostia (valves) of the dorsal vessel - areas of the heart called the periostial regions - where they phagocytose live and melanized pathogens. Although periostial hemocyte aggregation is an immune response that occurs following infection with bacteria and malaria parasites, the molecular basis of this process remains poorly understood. Here, we show that the thioester-containing proteins, TEP1, TEP3 and TEP4 are positive regulators of periostial hemocyte aggregation in the African malaria mosquito, Anopheles gambiae. RNAi-based knockdown of TEP1, TEP3 and TEP4 resulted in fewer periostial hemocytes following Escherichia coli infection, without affecting the adjacent population of non-periostial, sessile hemocytes. Moreover, knockdown of TEP1, TEP3 and TEP4 expression resulted in reduced bacterial accumulation and melanin deposition at the periostial regions. Finally, this study confirmed the role that TEP1 plays in reducing infection intensity in the hemocoel. Overall, this research shows that the complement-like proteins, TEP1, TEP3 and TEP4, are positive regulators of the functional integration between the immune and circulatory systems of mosquitoes.
蚊子的免疫和循环系统是功能上整合在一起的。在感染过程中，血体聚集在气门（瓣膜）周围的背血管 - 心脏的称为围心膜区域 - 在那里它们吞噬活的和黑化的病原体。尽管围心膜血体聚集是一种免疫反应，发生在细菌和疟原虫感染后，但这个过程的分子基础仍知之甚少。在这里，我们表明含硫酯蛋白 TEP1、TEP3 和 TEP4 是非洲疟蚊 Anopheles gambiae 中围心膜血体聚集的正调节剂。基于 RNAi 的 TEP1、TEP3 和 TEP4 敲低导致大肠杆菌感染后围心膜血体减少，而不影响相邻的非围心膜、固着血体群体。此外，TEP1、TEP3 和 TEP4 表达的敲低导致围心膜区域的细菌积累和黑色素沉积减少。最后，这项研究证实了 TEP1 在减少血腔感染强度中的作用。总的来说，这项研究表明补体样蛋白 TEP1、TEP3 和 TEP4 是蚊子免疫和循环系统功能整合的正调节剂。
