Infection Induces Expression of a Mosquito Salivary Protein (Agaphelin) That Targets Neutrophil Function and Inhibits Thrombosis without Impairing Hemostasis

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Malaria is transmitted by Plasmodium falciparum-infected Anopheles gambiae mosquitoes. Salivary gland contributes to the development of the parasite by creating a favorable environment for the infection and facilitating blood feeding and reproduction of the vector. However, the molecular mechanism by which the vector salivary gland modulates parasite/host interactions is not understood. We discovered that infection of the mosquito salivary gland upregulates several genes; among them, one codes for a protease inhibitor named Agaphelin. Notably, Agaphelin was found to exhibit multiple antihemostatic functions by targeting elastase. As a result, it inhibits platelet function which is required for blood to clot, and it prevents cleavage of TFPI, an anticoagulant that has recently been found to play a crucial role in thrombus formation in vivo. Agaphelin also attenuates neutrophils chemotaxis and the release of Neutrophil Extracellular Traps. These results provide evidence that neutrophils serve as a link between coagulation and the innate immune response. Agaphelin also exhibits anti-inflammatory and antithrombotic effects in vivo. Furthermore, Agaphelin did not promote bleeding, suggesting that targeting neutrophil exhibits potential therapeutic value. Altogether, these results highlight that the interplay between parasite, vector and host is a dynamic process that contributes and sustains the interface among Plasmodium, Anopheles and humans.

Vyšlo v časopise: Infection Induces Expression of a Mosquito Salivary Protein (Agaphelin) That Targets Neutrophil Function and Inhibits Thrombosis without Impairing Hemostasis. PLoS Pathog 10(9): e32767. doi:10.1371/journal.ppat.1004338
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004338

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