Mosquito SAMSP1 and SAMSP2 influence the initial stage of Plasmodium infection of mice

ABSTRACT This proposal will elucidate how two specific proteins in mosquito saliva influence the early stage of Plasmodium infection in mice. Our group previously developed a general screen to identify proteins in Anopheles gambiae saliva that associate with sporozoites during movement out the mosquito and deposition into the skin of a mammalian host (Schleicher Graham TR, Yang J, Freudzon M, Rembisz A, Craft S, Hamilton M, M, Mlambo G, Tripathi AK, Li Y, Cresswell P, Sinnis P, Dimopoulos G, Fikrig E. Nat Commun. 2018 25;9(1):2908). Several proteins were identified, including sporozoite-associated mosquito saliva protein (SAMSP) 1 and SAMSP2. Our preliminary data shows that SAMSP1 plays a role in facilitating Plasmodium infection in mice and that SAMSP2 has immunomodulatory activity. This proposal will now examine the importance of SAMSP1 and SAMPS2 in influencing the initial stage of Plasmodium infection in mice. Gene silencing and antibody blocking studies will assess the role of these proteins in the early stages of murine infection. In vivo two-photon microscopy of the dermis, and in vitro assays to assess movement and immune modulation, will delineate the effects of SAMSP1 and SAMSP2 on sporozoite activity. Understanding the importance of SAMSP1 and SAMSP2 in Plasmodium infection will hopefully lead to new strategies to combat malaria.