Martin Olivier

Biography

Member of McGill International TB Centre (RI-MUHC)

Research Interest

Integrity of IFN-gamma-induced signaling pathway (e.g. JAK2-STAT1alpha) regulating immune functions such as IL-12, MHC class I and II, is primordial for the development of effective host protection against infections involving protozoan parasites of Leishmania genus. However, once mononuclear phagocytes become infected with Ld several important macrophage functions involved in innate protection (e.g. Nitric oxide, oxygen radicals) and in the development of protective immune responses (e.g. IL-12 secretion, antigen processing and presentation through MHC class I and II) are inactivated to some extent. We recently reported that the IFN-gamma-inducible JAK2-STAT1alpha pathway was abnormal in Leishmania-infected cells. We further highlighted the importance of PTP SHP-1 in JAK2 inactivation that we showed to be rapidly triggered following parasite/macrophage interaction. In vitro and in vivo experiments performed with mice being deficient for the PTP SHP-1 have permitted to firmly establish that the PTP SHP-1 plays a pivotal role in Ld-induced macrophage dysfunctions and in installation and propagation of this parasite within its host. In parallel, we performed experiments representing the first demonstration that signaling inhibitors such as the PTPs inhibitors peroxovanadium compounds represent potential new therapic agents to modulate host immune response favoring a better control over different types of infection including leishmaniasis. Our present interest is to further our investigations to discover other negative regulatory mechanisms (e.g. Proteasome, phosphatases, surface receptors) modulated by Leishmania or other pathogens (Mycobacteria, Trypanosoma, Malaria, HCV) to subvert the innate immune response of the host and thus favoring pathogens installment and propagation. A better understanding of these mechanisms could conduct to the development of new therapy to control infectious agents.