Pala Zarna Rajeshkumar, Alves E Silva Thiago Luiz, Minai Mahnaz, Crews Benjamin, Patino-Martinez Eduardo, Carmona-Rivera Carmelo, Valenzuela-Leon Paola Carolina, Martin-Martin Ines, Flores-Garcia Yevel, Cachau Raul E, Srivastava Naman, Moore Ian N, Alves Derron A, Kaplan Mariana J, Fischer Elizabeth, Calvo Eric, Vega-Rodriguez Joel
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Infectious Disease Pathogenesis Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
bioRxiv. 2023 May 22:2023.05.22.541827. doi: 10.1101/2023.05.22.541827.
Mosquito salivary proteins play a crucial role in regulating hemostatic responses at the bite site during blood feeding. In this study, we investigate the function of salivary apyrase (AgApyrase) in transmission. Our results demonstrate that salivary apyrase interacts with and activates tissue plasminogen activator, facilitating the conversion of plasminogen to plasmin, a human protein previously shown to be required for transmission. Microscopy imaging shows that mosquitoes ingest a substantial amount of apyrase during blood feeding which reduces coagulation in the blood meal by enhancing fibrin degradation and inhibiting platelet aggregation. Supplementation of infected blood with apyrase significantly enhanced infection in the mosquito midgut. In contrast, AgApyrase immunization inhibited mosquito infection and sporozoite transmission. This study highlights a pivotal role for mosquito salivary apyrase for regulation of hemostasis in the mosquito blood meal and for transmission to mosquitoes and to the mammal host, underscoring the potential for new strategies to prevent malaria transmission.
蚊子唾液蛋白在吸血过程中调节叮咬部位的止血反应方面起着关键作用。在本研究中，我们调查了唾液腺苷三磷酸双磷酸酶（AgApyrase）在传播中的功能。我们的结果表明，唾液腺苷三磷酸双磷酸酶与组织纤溶酶原激活物相互作用并激活它，促进纤溶酶原转化为纤溶酶，纤溶酶是一种先前已证明在传播过程中必需的人类蛋白质。显微镜成像显示，蚊子在吸血过程中摄取了大量的腺苷三磷酸双磷酸酶，通过增强纤维蛋白降解和抑制血小板聚集来减少血餐中的凝血。用腺苷三磷酸双磷酸酶补充感染的血液显著增强了蚊子中肠的感染。相反，AgApyrase免疫抑制了蚊子感染和子孢子传播。这项研究突出了蚊子唾液腺苷三磷酸双磷酸酶在调节蚊子血餐中的止血以及向蚊子和哺乳动物宿主传播方面的关键作用，强调了预防疟疾传播新策略的潜力。
