Leishmania, macrophages and complement: a tale of subversion and exploitation.
Leishmania are intracellular protozoan parasites which reside primarily, if not exclusively, in host mononuclear phagocytes. Several studies have demonstrated that infectious promastigotes rapidly and efficiently fix complement when they encounter serum components during their transmission to the mammalian host. Activation of the complement system by a microorganism can have 3 distinct biological effects. First, fixation of the terminal complement components can result in complement-mediated lysis. Second, fixation of the 3rd component of complement can lead to opsonization of the organism for uptake by phagocytic cells. Finally, the elaboration of the complement anaphylotoxins, C3a and C5a, can lead to inflammation. In the present chapter, we discuss the interaction of leishmania promastigotes with the complement system. We show 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 complement to invade host mononuclear phagocytes efficiently. We discuss the mechanisms which allow metacyclic leishmania promastigotes to exploit the opsonic properties of complement and the receptors on macrophages involved in leishmania recognition. The role of complement mediated inflammatory processes in the host response to leishmania infection is an area which requires additional study.
Mosser
D M
DM
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Brittingham
A
A
D000818:Animals; D003167:Complement Activation; D003165:Complement System Proteins / Q000276:immunology*; D006790:Host-Parasite Interactions; D006801:Humans; D007891:Leishmania / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity*; D007896:Leishmaniasis / Q000276:immunology* / Q000469:parasitology; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology; D008666:Metalloendopeptidases / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D014774:Virulence
D003165:Complement System Proteins; D008666:Metalloendopeptidases; C055146:glycoprotein gp63, Leishmania