Distinct Melanization Pathways in the Mosquito Aedes aegypti

SummarySerine protease cascades are involved in blood coagulation and immunity. In arthropods, they regulate melanization, which plays an important role in immune defense and wound healing. However, the mechanisms underlying melanization pathways are not completely characterized. We found that in the mosquito Aedes aegypti, there are two distinct melanization activation pathways carried out by different modules of serine proteases and their specific inhibitors serpins. Immune melanization proteases (IMP-1 and IMP-2) and Serpin-1 mediate hemolymph prophenoloxidase cleavage and immune response against the malaria parasite. Tissue melanization, exemplified by the formation of melanotic tumors, is controlled by tissue melanization protease (CLIPB8), IMP-1, and Serpin-2. In addition, serine proteases CLIPB5 and CLIPB29 are involved in activation of Toll pathway by fungal infection or by infection-independent manner, respectively. Serpin-2 is implicated in the latter activation of Toll pathway. This study revealed the complexity underlying melanization and Toll pathway in mosquitoes.

► Distinct serine proteases and serpins regulate two mosquito melanization pathways
► Immune melanization is mediated by clip serine proteases IMP-1, IMP-2, and Serpin-1
► IMP-1 and IMP-2 are involved in mosquito defense against Plasmodium
► Tissue melanization is controlled by CLIPB8 (TMP), IMP-1, and Serpin-2