Immunization with AgTRIO, a Protein in Anopheles Saliva, Contributes to Protection against Plasmodium Infection in Mice

Abstract

SUMMARY Plasmodium infection begins with the bite of an anopheline mosquito, when sporozoites along with saliva are injected into a vertebrate host. The role of the host responses to mosquito saliva components in malaria remains unclear. We observed that antisera against Anopheles gambiae salivary glands partially protected mice from mosquito-borne Plasmodium infection. Specifically, antibodies to A. gambiae TRIO (AgTRIO), a mosquito salivary gland antigen, contributed to the protection. Mice administered AgTRIO antiserum showed lower Plasmodium liver burden and decreased parasitemia when exposed to infected mosquitoes. Active immunization with AgTRIO was also partially protective against Plasmodium berghei infection. A combination of AgTRIO antiserum and antibodies against Plasmodium circumsporozoite protein, a vaccine candidate, further decreased P. berghei infection. In humanized mice, AgTRIO antiserum afforded some protection against mosquito-transmitted Plasmodium falciparum. AgTRIO antiserum reduced the movement of sporozoites in the murine dermis. AgTRIO may serve as an arthropod-based target against Plasmodium to combat malaria.

Anopheles gambiae Lacking AgTRIO Inefficiently Transmits Plasmodium berghei to Mice

“…1B). To determine whether the level of AgTRIO protein was also decreased after dsAgTRIO injection, the salivary glands were collected from both groups and probed with AgTRIO rabbit antiserum (22). AgTRIO protein in the dsAgTRIO-injected group was decreased compared to the dsGluc-injected control group (Fig.…”

“…RNAi-mediated silencing of AgTRIO in A. gambiae results in a 60% decrease in AgTRIO transcript abundance. Based on our finding that immunization of mice with AgTRIO partially reduces Plasmodium infection (22), we hypothesized that AgTRIO plays a role during Plasmodium infection. AgTRIO was therefore silenced in mosquitoes to determine the importance of native AgTRIO in the pathogenesis of malaria.…”

“…Subsequently, the infectivity of sporozoites transmitted by mosquito bite appears to be more efficient than the infectivity of intravenously injected sporozoites (21), implying that interrelationships between saliva and Plasmodium facilitate the initial stage of infection. Indeed, passive immunization of mice with a high-titer antiserum against salivary gland extracts reduces the Plasmodium level during the initial stage of mosquito-borne infection (22), and antibodies directed against a specific protein in saliva, AgTRIO (AGAP001374), contribute to this effect (22). AgTRIO is expressed in salivary glands of Anopheles gambiae (23) and is significantly induced in salivary glands when Anopheles mosquitoes are infected with Plasmodium (22).…”

“…Indeed, passive immunization of mice with a high-titer antiserum against salivary gland extracts reduces the Plasmodium level during the initial stage of mosquito-borne infection (22), and antibodies directed against a specific protein in saliva, AgTRIO (AGAP001374), contribute to this effect (22). AgTRIO is expressed in salivary glands of Anopheles gambiae (23) and is significantly induced in salivary glands when Anopheles mosquitoes are infected with Plasmodium (22). Moreover, elevated AgTRIO expression levels are related to insecticide resistance in A. gambiae with a mutation in acetylcholinesterase (24), and silencing AgTRIO does not influence probing or blood feeding by Anopheles gambiae mosquitoes (25).…”

Identification of Plasmodium falciparum proteoforms from liver stage models

“…Towards identification of liver stage malaria proteoforms this study first analysed parasite growth characteristics in state-of-the-art experimental liver stage models including PHHs grown in vitro and human liver chimeric (FNRG) mice [26,[28][29][30]. Primary human hepatocytes were transplanted into FNRG mice which after several weeks became highly engrafted as seen by ~ 1 × 10 4 µg/ Figure S1).…”