title: Subversion mechanisms by which Leishmania parasites can escape the host immune response: a signaling point of view.
abstract: The obligate intracellular parasite Leishmania must survive the antimicrobial activities of its host cell, the macrophage, and prevent activation of an effective immune response. In order to do this, it has developed numerous highly successful strategies for manipulating activities, including antigen presentation, nitric oxide and oxygen radical generation, and cytokine production. This is generally the result of interactions between Leishmania cell surface molecules, particularly gp63 and LPG, and less well identified macrophage surface receptors, causing the distortion of specific intracellular signaling cascades. We describe some of the signaling pathways and intermediates that are repressed in infected cells, including JAK/STAT, Ca(2+)-dependent protein kinase C (PKC) isoforms, and mitogen-activated protein kinases (especially ERK1/2), and proteasome-mediated transcription factor degradation. We also discuss protein tyrosine phosphatases (particularly SHP-1), intracellular Ca2+, Ca(2+)-independent PKC, ceramide, and the suppressors of cytokine signaling family of repressors, which are all reported to be activated following infection, and the role of parasite-secreted cysteine proteases.
authors.affiliation: Centre for the Study of Host Resistance at the Research Institute of the McGill University Health Centre, Montréal, Québec, Canada. martin.olivier@mcgill.ca
authors.forename: Martin
authors.initials: M
authors.lastname: Olivier
authors.forename: David J
authors.initials: DJ
authors.lastname: Gregory
authors.forename: Geneviève
authors.initials: G
authors.lastname: Forget
mesh_terms: D000818:Animals; D006801:Humans; D007891:Leishmania / Q000254:growth & development / Q000472:pathogenicity*; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology*; D010587:Phagocytosis; D011506:Proteins / Q000378:metabolism; D015800:Protozoan Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D011506:Proteins; D015800:Protozoan Proteins