Anopheles stephensi salivary glands bear receptors for region I of the circumsporozoite protein of Plasmodium falciparum

Abstract

In the mosquito, Plasmodium sporozoites rupture from oocysts found on the midgut wall, circulate in the hemolymph and invade salivary glands where they wait to be injected into a vertebrate host during a bloodmeal. The mechanisms by which sporozoites specifically attach to and invade salivary glands are not known but evidence suggests that it is a receptor-mediated process. Here we show that the major surface protein of sporozoites, the circumsporozoite protein (CS), binds preferentially to salivary glands when compared to other organs exposed to the circulating hemolymph. In addition, we show that a peptide encompassing region I, a highly conserved sequence found in all rodent and primate Plasmodium CS proteins, inhibits binding of CS to mosquito salivary glands.

Antigenic Diversity of the Plasmodium vivax Circumsporozoite Protein in Parasite Isolates of Western Colombia

“…5 These flanking regions contain short, highly conserved sequences denoted as Region I (RI) and RII regions, 3 that are the binding domains for glycosaminoglycan heparin sulfate receptors, which are found on the surface of hepatocytes 6 and mosquito salivary glands. 7 The RI and RII domains appear to play important roles in parasite invasion to host cells, both in the mosquito and the vertebrate host. 7,8 The CR of Plasmodium vivax CS protein has been shown to be dimorphic, characterized by tandem repeats of the nonapeptide GDRADGQPA in the VK210 sequence, 5 and ANGAGNQPG that corresponds to the VK247 variant sequence.…”

“…7 The RI and RII domains appear to play important roles in parasite invasion to host cells, both in the mosquito and the vertebrate host. 7,8 The CR of Plasmodium vivax CS protein has been shown to be dimorphic, characterized by tandem repeats of the nonapeptide GDRADGQPA in the VK210 sequence, 5 and ANGAGNQPG that corresponds to the VK247 variant sequence. 9 Both nonapeptides sequences are repeated ~20 times in their corresponding proteins; however, there is extensive polymorphism with regard to the number of repeats.…”

Transgenic Plasmodium berghei sporozoites expressing β-galactosidase for quantification of sporozoite transmission

“…Sporozoites are formed in a complex process, termed sporogony, that represents the longest developmental phase of the Plasmodium life cycle [3]. Although sporozoites are likely passively transported throughout the hemocoel, there is evidence that they specifically recognize the salivary glands through a receptor-mediated process [4][5][6][7]. Sporozoites breach the basal lamina and acinar gland cells and accumulate in the salivary duct [8].…”

A proteomic analysis of salivary glands of femaleAnopheles gambiae mosquito

“…It has been previously shown that sporozoite-salivary gland interaction is species specific and receptor mediated; the glands being involved in both recognition and invasion [5]. It is also known that sporozoites only invade the distal parts of median and lateral lobes of female salivary glands and that recombinant circumsporozoite (CS) protein binds specifically to Anopheles stephensi salivary glands, particularly to the median and distal lateral lobes of the gland [6]. Mosquito saliva contains a large number of biomolecules responsible for antihemostatic activity, which assist hematophagous arthropods during the feeding process [7].…”