Malaria oocysts require circumsporozoite protein to evade mosquito immunity.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35680915.
- Also identified by DOI 10.1038/s41467-022-30988-z and PMC identifier 9184642.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Malaria parasites are less vulnerable to mosquito immune responses once ookinetes transform into oocysts, facilitating parasite development in the mosquito. However, the underlying mechanisms of oocyst resistance to mosquito defenses remain unclear. Here, we show that circumsporozoite protein (CSP) is required for rodent malaria oocysts to avoid mosquito defenses. Mosquito infection with CSP<sub>mut</sub> parasites (mutation in the CSP pexel I/II domains) induces nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 5 (NOX5)-mediated hemocyte nitration, thus activating Toll pathway and melanization of mature oocysts, upregulating hemocyte TEP1 expression, and causing defects in the release of sporozoites from oocysts. The pre-infection of mosquitoes with the CSP<sub>mut</sub> parasites reduces the burden of infection when re-challenged with CSP<sub>wt</sub> parasites by inducing hemocyte nitration. Thus, we demonstrate why oocysts are invisible to mosquito immunity and reveal an unknown role of CSP in the immune evasion of oocysts, indicating it as a potential target to block malaria transmission.
Medical subject headings
- Culicidae
- Malaria