Cell biology of host-parasite membrane interactions in leishmaniasis

Molecular interactions at the host-parasite interface are crucial for the outcome of microbial infection, particularly in infection by intracellular parasites, such as Leishmania donovani and Leishmania mexicana, whose natural transmission begins with the delivery of the promastigote stage by the sandfly vector into the susceptible host. The ensuing event is intracellular parasitism of macrophages in the host by the amastigote stage. The establishment of this event in leishmaniasis must follow the sequence: (1) Leishmania-macrophage attachment; (2) entry of Leishmania species into macrophages; (3) intra-macrophage survival and differentiation of Leishmania species; and (4) intracellular multiplication of Leishmania species. This sequence precedes all clinical symptoms and pathological consequences in different forms of the disease. Study of these cellular events in Leishmania-macrophage systems in vitro indicates that host-parasite membrane interactions dictate many of the cellular events. Some morphological and functional changes of macrophages in response to leishmanial infection are related to their membrane activities, i.e. endocytosis and exocytosis. Leishmania parasites undergo profound plasma membrane-related changes, on entry into macrophages, at the morphological, antigenic and molecular levels. Most of these changes probably reflect necessary steps for the transition of Leishmania species from an extracellular to an intracellular life. The remarkable ability of Leishmania species subsequently to live in the secondary lysosome of the macrophage may also be due to certain intrinsic structures and dynamic properties of the parasite plasma membrane. Further analysis of leishmanial surface molecules and their interactions with macrophages is essential in any attempt to understand the pathogenic mechanism in leishmaniasis.