| Autor: |
Thiago Luiz Alves e Silva, Gaspar E. Canepa, Brendan Sweeney, Patricia Hessab Alvarenga, Ming Zhao, Joel Vega-Rodríguez, Alvaro Molina-Cruz, Carolina Barillas-Mury |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Microbiology Spectrum, Vol 11, Iss 6 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2165-0497 |
| DOI: |
10.1128/spectrum.00940-23 |
| Popis: |
ABSTRACT The mosquito immune system limits Plasmodium infection and malaria transmission. Plasmodium falciparum evades the mosquito defense response by expressing the surface protein P. falciparum P47 (Pfs47) that inhibits midgut epithelial nitration by interacting with the mosquito midgut P47 receptor (P47Rec). However, the mechanism by which P47Rec suppresses caspase-mediated nitration is unknown. Here, we show that epithelial invasion by Pfs47 knockout parasites is followed by an extrusion of cells undergoing caspase-mediated apoptosis, which triggers the release of hemocyte-derived microvesicles (HdMv’s), known to promote complement activation and ookinete lysis. In contrast, invasion by P. falciparum parasites that express Pfs47 accelerates the extrusion of damaged cells and disrupts caspase activation and HdMv release. The Anopheles gambiae heat shock protein 70 cognate 3 (Hsc70-3), the ortholog of Drosophila binding immunoglobulin protein, was identified as a molecular partner of P47Rec. Silencing of Hsc70-3 promotes lysis of Pfs47 wild-type parasites through a caspase S2-dependent mechanism. The interaction of P47Rec activates a Hsc70-3-mediated anti-apoptotic response that prevents caspase activation. The interaction of P47Rec with Hsc70-3 is necessary for P. falciparum to evade the mosquito early immune responses that target the ookinete stage. IMPORTANCE Malaria transmission by Anopheles gambiae mosquitoes is very effective, in part because the parasite expresses a surface protein called Pfs47 that allows it to evade the mosquito immune system. Here we investigate how this protein changes the response of mosquito midgut epithelial cells to invasion by the parasite. Pfs47 is known to interact with P47Rec, a mosquito midgut receptor. We found that Pf47Rec inhibits caspase-mediated apoptosis by interacting with the Hsc70-3. This disrupts nitration of midgut epithelial cells invaded by the parasite and the release of hemocyte-derived microvesicles, which are critical for effective activation of the mosquito complement system that eliminates the parasite. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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