Imaging mosquito transmission of Plasmodium sporozoites into the mammalian host: immunological implications

The malaria infection is initiated in mammals by injection of the sporozoite stage of the parasite through the bite of Plasmodium-infected, female Anopheles mosquitoes. Sporozoites are injected into extravascular portions of the skin while the mosquito is probing for a blood source. Sporozoite gliding motility allows them to locate and penetrate blood vessels of the dermis or subcutaneous tissues; once in the blood, they reach the liver, within which they continue their development. Some of the injected parasites invade dermal lymph vessels and travel to the proximal draining lymphatic node, where they interact with host immunocytes. The host responds to viable or attenuated sporozoites with antibodies directed against the immunodominant circumsporozoite protein (CSP), as well as against other sporozoite proteins. These CSP antibodies can inhibit the numbers of sporozoites injected by mosquitoes and the motility of those injected into the skin. This first phase of the immune response is followed by cell-mediated immunity involving CD8 T-cells directed against the developing liver stage of the parasite. This review discusses the early history of imaging studies, and focuses on the role that imaging has played in enabling a better understanding of both the induction and effector functions of the immune responses against sporozoites.