Professor and Director of the Centre
531 boul. des Prairies, Laval
(Québec) H7V 1B7
Because of their potent microbicidal and tumoricidal capacities, macrophages play a major role in the immune response. Macrophage functions are not constitutive, being rather acquired (activation) in the presence of molecules such as cytokines or microbial-derived products. Binding of these molecules at the surface of a resting macrophage triggers intracellular signalling pathways, which culminate in the acquisition of phenotypes allowing the macrophage to perform specific immune functions. One of my objectives is to gain a better knowledge of the molecular mechanisms leading to macrophage activation in the context of host defense. We concentrate our efforts on the role of a family of kinases known as protein kinase C (PKC), which play a key role in intracellular signalling.
We also investigate the interaction between the intracellular parasite Leishmania and the macrophage. Leishmania evolved various strategies to avoid or manipulate host immune defenses. One of these strategies consists in modulating host cell intracellular signalling pathways. Since Leishmania interferes with macrophage activation through inhibition of PKCs, studying the underlying mechanisms will enhance our understanding of macrophage function regulation. Another strategy used by intracellular parasites, including the promastigote form of Leishmania, consists in remodelling the vacuole in which they replicate. Defining the underlying mechanisms will contribute to our knowledge of basic microbial pathogenesis problems..
Vinet AF, Jananji S, Turco SJ, Fukuda M, Descoteaux A.
Exclusion of synaptotagmin V at the phagocytic cup by Leishmania donovani lipophosphoglycan results in decreased promastigote internalization. Microbiology. 2011 Sep;157(Pt 9):2619-28. Epub 2011 Jun 16.
Gabriel C, McMaster WR, Girard D, Descoteaux A.
Leishmania donovani promastigotes evade the antimicrobial activity of neutrophil extracellular traps. J Immunol. 2010 Oct 1;185(7):4319-27. Epub 2010 Sep 8.
Matte C, Descoteaux A.
Leishmania donovani amastigotes impair gamma interferon-induced STAT1alpha nuclear translocation by blocking the interaction between STAT1alpha and importin-alpha5. Infect Immun. 2010 Sep;78(9):3736-43. Epub 2010 Jun 21.
Vinet AF, Descoteaux A.
Leishmania donovani delays phagolysosomal acidification. Med Sci (Paris). 2010 Mar;26(3):227-8. French. No abstract available.
Vinet AF, Fukuda M, Turco SJ, Descoteaux A.
The Leishmania donovani lipophosphoglycan excludes the vesicular proton-ATPase from phagosomes by impairing the recruitment of synaptotagmin V. PLoS Pathog. 2009 Oct;5(10):e1000628. Epub 2009 Oct 16.
Hardy PO, Diallo TO, Matte C, Descoteaux A.
Roles of phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase in the regulation of protein kinase C-alpha activation in interferon-gamma-stimulated macrophages. Immunology. 2009 Sep;128(1 Suppl):e652-60. Epub 2009 Jan 23.