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Albert Descoteaux

Academic title(s): 

Professor


Université du Québec

Albert Descoteaux
Contact Information
Address: 

INRS-Institut Armand Frappier
Université du Québec
531 des Prairies boulevard
Laval, QC H7V 1B7
Tel: (450) 687-5010 ext. 4465
Fax: (450) 686-5501

Email address: 
albert.descoteaux [at] iaf.inrs.ca
Division: 
Adjunct Members
Location: 
Université du Québec
Current research: 

Macrophage activation; Leishmania-macrophage interaction.Ìý

​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, leading to the induction of gene expression and protein synthesis. These intracellular events 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. This is essential for the development of novel pharmacological approaches based on the selective manipulation of intracellular signalling pathways. We concentrate our efforts on the role of a family of kinases known asÌýprotein kinase CÌý(±Ê°­°ä).

PKCs play a key role in intracellular signalling and the regulation of gene expression. To determine to which extent individual PKC isoenzymes regulate macrophage activity, we are genetically modifying macrophage cell lines to overproduce active PKC isoenzymes, as well as dominant-negative PKC mutants.

We also investigate the interaction between the intracellular parasiteÌý³¢±ð¾±²õ³ó³¾²¹²Ô¾±²¹Ìýand the macrophage. Although the inside of a macrophage seems inhospitable, several intracellular microbes chose the macrophage as a host cell. Of course, these microbes evolved strategies to avoid or manipulate host immune defenses.

One of these strategies consists in modulating in their favor their host cell intracellular signalling pathways. SinceÌý³¢±ð¾±²õ³ó³¾²¹²Ô¾±²¹Ìýinterferes with macrophage activation through inhibition of PKCs, studying the underlying mechanisms will enhance our understanding of macrophage function regulation.

Finally, in the macrophage,ÌýLeishmaniaÌýresides within a lysosomal vacuole. Using genetically definedÌýLeishmaniavirulence mutants, we have shown that this parasite can modulate the biogenesis of their vacuole using surface glycolipids. Defining the molecular composition of vacuoles induced by virulence mutants will contribute to our knowledge of basic microbial pathogenesis problems.

Selected publications: 
  • .Ìý2003. "IFN-gamma-induced MHC class II expression: transactivation of CIITA promoter IV by IRF-1 is regulated by protein kinase C-alpha."ÌýJournal of ImmunologyIn press
  • Ìý2003. "Role of protein kinase C-alpha for uptake of unopsonized prey and phagosomal maturation in macrophages."ÌýBiochemical and Biophysical Research CommunicationsÌý302: 653-658.
  • Ìý2002. "Modulation of lipopolysaccharide-induced NF-IL6 activation by protein kinase C-alpha in a mouse macrophage cell line." EuropeanÌýJournal of ImmunologyÌý32: 2897-2904
  • Ìý2002. "³¢±ð¾±²õ³ó³¾²¹²Ô¾±²¹ÌýLPG3 is a GRP94 homolog required for synthesis of phosphoglycans implicated in parasite virulence but not viability."ÌýThe EMBO JournalÌý21: 4458-4469
  • Ìý2002. "Protein kinase C-zeta regulates, via NF-kB, the IL-1 and TNF-a induced transcription of the matrix metalloproteinase-9 gene in glioma cells."ÌýJournal of Biological ChemistryÌý277: 35150-35155
  • Ìý2001. "Leishmania donovanilipophosphoglycan causes periphagosomal actin accumulation: correlation with impaired translocation of PK C-alpha and defective phagosome maturation."ÌýCellular MicrobiologyÌý3: 439-447.
  • 2000. "Rab5 regulates the kiss and run fusion between phagosomes and endosomes and the acquisition of phagosome leishmanicidal properties in RAW 264.7 macrophages."ÌýJournal of Cell ScienceÌý113: 3531-3541
  • Ìý2000. "Cyclooxygenase-2 expression in macrophages: regulation by protein kinase C-alpha."ÌýJournal of ImmunologyÌý165: 3985-3991
  • Ìý2000. "Leishmania donovani promastigotesÌýevade the activation of mitogen-activated protein kinases p38, c-Jun N-terminal kinase, and extracellular signal-regulated kinase-1/2 during infection of naive macrophages."ÌýEuropean Journal of ImmunologyÌý30: 2235-2244
  • 2000. Leishmania promastigotes require lipophosphoglycan to actively modulate the fusion properties of phagosomes at an early step of phagocytosis.ÌýCellular MicrobiologyÌý2: 115-126.
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