The fibrinolytic system enables the onset of Plasmodium infection in the mosquito vector and the mammalian host

Thiago Luiz Alves Silva, Andrea Radtke, Amanda Balaban, Tales Vicari Pascini, Zarna Rajeshkumar Pala, Alison Roth, Patricia H. Alvarenga, Yeong Je Jeong, Janet Olivas, Anil K. Ghosh, Hanhvy Bui, Brandon S. Pybus, Photini Sinnis, Marcelo Jacobs-Lorena, Joel Vega-Rodríguez

Research output: Contribution to journalArticlepeer-review

Abstract

Plasmodium parasites must migrate across proteinaceous matrices to infect the mosquito and vertebrate hosts. Plasmin, a mammalian serine protease, degrades extracellular matrix proteins allowing cell migration through tissues. We report that Plasmodium gametes recruit human plasminogen to their surface where it is processed into plasmin by corecruited plasminogen activators. Inhibition of plasminogen activation arrests parasite development early during sexual reproduction, before ookinete formation. We show that increased fibrinogen and fibrin in the blood bolus, which are natural substrates of plasmin, inversely correlate with parasite infectivity of the mosquito. Furthermore, we show that sporozoites, the parasite form transmitted by the mosquito to humans, also bind plasminogen and plasminogen activators on their surface, where plasminogen is activated into plasmin. Surface-bound plasmin promotes sporozoite transmission by facilitating parasite migration across the extracellular matrices of the dermis and of the liver. The fibrinolytic system is a potential target to hamper Plasmodium transmission.

Original languageEnglish (US)
Article numbereabe3362
JournalScience Advances
Volume7
Issue number6
DOIs
StatePublished - Feb 5 2021
Externally publishedYes

ASJC Scopus subject areas

  • General

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