title: Modulation of the phagosome proteome by interferon-gamma.
abstract: Macrophages are immune cells that function in the clearance of infectious particles. This process involves the engulfment of microbes into phagosomes where these particles are lysed and degraded. In the current study, we used a large scale quantitative proteomics approach to analyze the changes in protein abundance induced on phagosomes by interferon-gamma (IFN-gamma), an inflammatory cytokine that activates macrophages. Our analysis identified 167 IFN-gamma-modulated proteins on phagosomes of which more than 90% were up-regulated. The list of phagosomal proteins regulated by IFN-gamma includes proteins expected to alter phagosome maturation, enhance microbe degradation, trigger the macrophage immune response, and promote antigen loading on major histocompatibility complex (MHC) class I molecules. A dynamic analysis of IFN-gamma-sensitive proteins by Western blot indicated that newly formed phagosomes display a delayed proteolytic activity coupled to an increased recruitment of the MHC class I peptide-loading complex. These phagosomal conditions may favor antigen presentation by MHC class I molecules on IFN-gamma-activated macrophages.
authors.affiliation: Département de pathologie et biologie cellulaire, Université de Montréal, 2900 Edouard-Montpetit, Montréal, Québec H3T 1J4, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Jutras
authors.forename: Mathieu
authors.initials: M
authors.lastname: Houde
authors.forename: Nathan
authors.initials: N
authors.lastname: Currier
authors.forename: Jonathan
authors.initials: J
authors.lastname: Boulais
authors.forename: Sophie
authors.initials: S
authors.lastname: Duclos
authors.forename: Sylvie
authors.initials: S
authors.lastname: LaBoissière
authors.forename: Eric
authors.initials: E
authors.lastname: Bonneil
authors.forename: Paul
authors.initials: P
authors.lastname: Kearney
authors.forename: Pierre
authors.initials: P
authors.lastname: Thibault
authors.forename: Eustache
authors.initials: E
authors.lastname: Paramithiotis
authors.forename: Patrice
authors.initials: P
authors.lastname: Hugo
authors.forename: Michel
authors.initials: M
authors.lastname: Desjardins
mesh_terms: D000818:Animals; D002460:Cell Line; D002853:Chromatography, Liquid; D045142:Cross-Priming / Q000187:drug effects; D015180:Electrophoresis, Gel, Two-Dimensional; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology*; D013058:Mass Spectrometry; D051379:Mice; D010588:Phagosomes / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*
chemical_list: D015395:Histocompatibility Antigens Class I; D020543:Proteome; D007371:Interferon-gamma