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Updated: Jun 12, 2025
A Bacterial Oral Feeding Assay with Antibiotic-Treated Mosquitoes
Published on: September 12, 2020
Host complement C3 promotes malaria transmission by killing symbiotic bacteria in the mosquito midgut
Abstract:
Host-derived factors ingested during mosquito blood feeding are poorly understood modulators of malaria transmission. Here, we demonstrated that host complement C3, acquired by mosquitoes during Plasmodium infection, significantly enhanced rodent malaria infection in laboratory-reared mosquitoes. This effect was recapitulated in field-caught Anopheles sinensis mosquitoes, confirming its relevance to malaria transmission in a more natural setting. Moreover, host-derived C3 significantly reduced the efficacy of anti-Pfs25 antibodies in blocking malaria transmission. Mechanistically, host-derived C3 lyses the mosquito midgut symbiont Elizabethkingia anophelis (E. anophelis)-a bacterium that intrinsically suppresses parasite development by blocking the zygote-to-ookinete transition. Strikingly, host-derived C3 in mosquitoes appears to be activated by the alternative pathway, and inhibiting Factor B with Iptacopan (LNP023) reduced Plasmodium falciparum (P. falciparum) infection, while increased the efficacy of anti-Pfs25 antibodies to blocking P. falciparum transmission in the standard membrane-feeding assay. Therefore, this study describes a strategy of the malaria parasite to utilize host complement C3 to promote its transmission and provides us with an avenue to block malaria transmission and improve the blocking efficacy of anti-Pfs25 antibodies by the inhibition of C3 activation.
Insights
Malaria parasites exploit host complement C3 to enhance mosquito infection and reduce antibody effectiveness. Inhibiting C3 activation with Iptacopan offers a new strategy to block malaria transmission.
Area of Science:
- Malariology
- Immunology
- Vector Biology
Background:
- Host-derived factors influencing malaria transmission are not fully understood.
- Mosquitoes ingest blood meals containing various host components during pathogen transmission.
Purpose of the Study:
- To investigate the role of host complement C3 in modulating malaria parasite infection in mosquitoes.
- To explore the potential of targeting host C3 for malaria transmission blocking strategies.
Main Methods:
- Experimental infection of laboratory and field-caught mosquitoes with Plasmodium.
- Administration of complement inhibitors (Iptacopan) and anti-Pfs25 antibodies.
- Standard membrane-feeding assays to assess transmission efficiency.
Main Results:
- Host-derived complement C3 acquired during blood feeding significantly enhanced Plasmodium infection in mosquitoes.
- Host C3 reduced the efficacy of anti-Pfs25 antibodies in blocking malaria transmission.
- Host C3 was found to lyse the mosquito symbiont Elizabethkingia anophelis, which normally suppresses parasite development.
- Inhibition of complement Factor B with Iptacopan reduced Plasmodium falciparum infection and enhanced anti-Pfs25 antibody efficacy.
Conclusions:
- Plasmodium parasites utilize host-derived complement C3 to promote their transmission.
- Inhibiting C3 activation presents a novel therapeutic avenue for blocking malaria transmission.
- Targeting host C3 can improve the effectiveness of transmission-blocking antibodies.
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