Interactions Between Leishmania and the Host Macrophage
Martin Olivier and David J. Gregory
from: Leishmania: After The Genome (Edited by: Peter J. Myler and Nicolas Fasel). Caister Academic Press, U.K. (2008)
In this chapter, we address the relationship between Leishmania and its host macrophage at the molecular level. From the initial interactions between receptor proteins on the macrophage membrane and Leishmania surface molecules, the parasite modulates the activities of the macrophage's intracellular signalling pathways for its own ends. Protein tyrosine phosphatases, particularly SHP-1, are rapidly activated, and intracellular Ca2+ and ceramide concentrations are elevated. These, and other factors, lead to inhibition of JAK2, MAP Kinase and Protein Kinase C pathways. Moreover, recent studies have shown that the transcription factor STAT1α is degraded by the proteasome, and proteolytic mechanisms also regulate the NF-κB family. These pathways allow Leishmania to radically alter the behaviour of its host cell without ever leaving the phagolysosome. In particular, production of microbicidal molecules (especially nitric oxide and reactive oxygen intermediates) and activating cytokines (e.g. IL-1, IL-12 and TNFα) is inhibited, whereas secretion of immunosuppressive molecules and certain chemokines (e.g. TGFβ, PGE2 and MIP-2) is increased. Infected macrophages become non-responsive to activating stimuli such as IFNγ, and a number of mechanisms interfere with antigen presentation. We discuss the molecular details of all these processes as revealed by recent studies, and their important contribution to the survival of Leishmania in the host read more ...