Malaria oocysts require circumsporozoite protein to evade mosquito immunity

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 CSPmut 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 CSPmut parasites reduces the burden of infection when re-challenged with CSPwt 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. Circumsporozoite protein (CSP), the major surface protein of Plasmodium sporozoites, is important for parasite targeting to mosquito salivary glands and the mammalian liver. Here, Zhu et al. show that CSP is required for rodent malaria oocysts to evade mosquito immunity by inducing hemocyte nitration and causing subsequent defects in sporozoite-release from oocysts.

Automated summary

A study showed that malaria parasite oocysts evade mosquito immune responses by inducing hemocyte nitration. This finding is important for understanding the immune evasion mechanisms of oocysts and highlights the unknown role of CSP in this process.