Parasitic adaptive mechanisms in infection by Leishmania

Leishmania are a resilient group of intracellular parasites that infect macrophages. The resultant complex of diseases, or leishmaniases, caused by the parasites affect over twelve million people worldwide. Leishmania have developed unique adaptive mechanisms to ensure their survival in the harsh environments faced throughout their life cycle. These parasites must not only contend with the hostile digestive conditions found within the sand fly vector, but they must also avoid destruction by the host immune system while in the bloodstream, before entering the macrophage. To do so, Leishmania express unique lipophosphoglycan (LPG) molecules and the metalloprotease gp63, among other proteins, on their cell surface. To enter the macrophage, Leishmania utilizes a variety of cellular receptors to mediate endocytosis. Once inside the macrophage, Leishmania is protected from phagolysosome degradation by a variety of adaptations to inhibit cellular defense mechanisms. These include the inhibition of phagosome-endosome fusion, hydrolytic enzymes, cell signaling pathways, nitric oxide production, and cytokine production. While other parasites can also infect macrophages, Leishmania is distinctive in that it not only relies on its own defenses to survive and reproduce within the macrophage phagolysosome, but Leishmania also manipulates the host immune response in order to protect itself and to gain entry into the cell. These unique adaptive mechanisms help promote Leishmania survival. (C) 2002 Elsevier Science (USA).