The Phagosomal Proteome in Interferon-[gamma]-Activated Macrophages

The ability of macrophages to clear pathogens and elicit a sustained immune response is regulated by various cytokines, including interferon-γ (IFN-γ). To investigate the molecular mechanisms by which IFN-γ modulates phagosome functions, we profiled the changes in composition, abundance, and phospho...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2009-01, Vol.30 (1), p.143
Main Authors: Trost, Matthias, English, Luc, Lemieux, Sébastien, Courcelles, Mathieu, Desjardins, Michel, Thibault, Pierre
Format: Article
Language:English
Subjects:
Kinases
Medical research
Microorganisms
Phosphorylation
Proteins
Proteomics
Rodents
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Summary:The ability of macrophages to clear pathogens and elicit a sustained immune response is regulated by various cytokines, including interferon-γ (IFN-γ). To investigate the molecular mechanisms by which IFN-γ modulates phagosome functions, we profiled the changes in composition, abundance, and phosphorylation of phagosome proteins in resting and activated macrophages by using quantitative proteomics and bioinformatics approaches. We identified 2415 phagosome proteins together with 2975 unique phosphorylation sites with a high level of sensitivity. Using network analyses, we determined that IFN-γ delays phagosomal acquisition of lysosomal hydrolases and peptidases for the gain of antigen presentation. Furthermore, this gain in antigen presentation is dependent on phagosomal networks of the actin cytoskeleton and vesicle-trafficking proteins, as well as Src kinases and calpain proteases. Major histocompatibility complex class I antigen-presentation assays validated the molecular participation of these networks in the enhanced capacity of IFN-γ-activated macrophages to crosspresent exogenous antigens to CD8+T cells.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2008.11.006