LEISHMANIA, MACROPHAGES AND COMPLEMENT - A TALE OF SUBVERSION AND EXPLOITATION

Leishmania are intracellular protozoan parasites which reside primaril y, if not exclusively, in host mononuclear phagocytes. Several studies have demonstrated that infectious promastigotes rapidly and efficient ly fix complement when they encounter serum components during their tr ansmission to the mammalian host. Activation of the complement system by a microorganism can have 3 distinct biological effects. First, fixa tion of the terminal complement components can result in complement-me diated lysis. Second, fixation of the 3rd component of complement can lead to opsonization of the organism far uptake by phagocytic cells. F inally, the elaboration of the complement anaphylotoxins, C3a and C5a, can lead to inflammation. In the present chapter, we discuss the inte raction of leishmania promastigotes with the complement system. We sho w that infectious promastigotes avoid the lytic effects of complement and resist fixation of the terminal complement components. At the same time, however, these organisms depend on fixation of opsonic compleme nt to invade host mononuclear phagocytes efficiently. We discuss the m echanisms which allow metacyclic leishmania promastigotes to exploit t he opsonic properties of complement and the receptors on macrophages i nvolved in leishmania recognition. The role of complement mediated inf lammatory processes in the host response to leishmania infection is an area which requires additional study.