Infected host serum blocks transmission of Plasmodium yoelii via a nitric oxide-dependent mechanism

Abstract

The present study was carried out to clarify whether NO mediates the `crisis serum' induced transmission-blocking of Plasmodium yoelii to the mosquito vector. Mouse serum, obtained 5 days after P. yoelii infection (D5 serum), was administered intravenously into the mice 3 days after P. yoelii infection, followed 4–8 h later by a mosquito feed. The D5 serum demonstrated a marked suppression of oocyst development. Four hours after D5 serum injection to the mice on day 3 after P. yoelii infection, spleens were removed from the mice, and increased levels of nitrite were observed in the spleen cell culture supernatants. The contribution of NO to the D5 serum induced suppression of oocyst formation was investigated using l-NMMA, a selective inhibitor of nitric oxide synthase. The reduction of oocyst formation in the mosquito midgut caused by the injection of D5 serum was reversed by the administration of l-NMMA to the mice. Moreover, malaria parasitized red blood cell extract possessing the ability to induce NO in mouse spleens also showed the same inhibitory effects on oocyst formation as D5 serum. Together, these results suggest that the D5 serum may contain a parasitized red blood cell derived substance(s) which induce the NO production from host effector cells, and then inhibits the transmission of malaria parasites to the mosquito vector.