Investigations of complement resistance factors in <i>Leishmania chagasi</i>
Leishmania are protozoan parasites that are the causative agents of a group of diseases collectively termed leishmaniasis, which range in severity of clinical manifestation from ulcerative skin lesions developing at the location of the insect bite, known as cutaneous leishmaniasis (CL) to disseminated, life threatening, visceral infection, known as visceral leishmaniasis (VL). These diverse clinical manifestations are determined by both the infecting species of Leishmania and the immune response of the host . Leishmania parasites are transmitted to mammals, including humans, by the bite of phlebotomine sand flies and are capable of infecting nearly all vertebrates. They are unicellular, eukaryotic pathogens with a digenetic lifecycle, alternating between and replicating within an insect vector and a mammalian host. Leishmania exist within the sand fly vector as motile, extra-cellular promastigotes. In a mammalian host, Leishmania exist as nonmotile, spherical amastigotes that reside and proliferate within the phagolysosome of macrophages. When a sand fly ingests a blood meal from an infected host, the amastigotes are passed to the insect within ingested macrophages. As the macrophages lyse, the amastigotes are released into the midgut of the fly and quickly differentiate into the motile, flagellated form of the parasite called the procyclic promastigote. These promastigotes adhere to the midgut epithelium and are retained as the blood meal is digested and excreted. The procyclic promastigotes begin to divide and transform into additional promastigote forms, eventually leading to the generation of virulent, non-dividing metacyclics, capable of establishing infection in a successive host. The following work describes efforts to gain a more complete understanding of the process of metacyclogenesis, the process by which the infectious promastigotes are generated within the sand fly vector. Studies of infectious and culture modified parasites are used to identify and characterize factors involving one particular aspect of metacyclogenesis, resistance to lysis by complement factors in human serum.