The phagosomal proteome in interferon-gamma-activated macrophages

Matthias Trost, Luc English, Sebastien Lemieux, Mathieu Courcelles, Michel Desjardins (Lead / Corresponding author), Pierre Thibault (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    166 Citations (Scopus)

    Abstract

    The ability of macrophages to clear pathogens and elicit a sustained immune response is regulated by various cytokines, including interferon-gamma (IFN-gamma). To investigate the molecular mechanisms by which IFN-gamma 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-gamma 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-gamma-activated macrophages to crosspresent exogenous antigens to CD8(+) T cells.

    Original languageEnglish
    Pages (from-to)143-154
    Number of pages12
    JournalImmunity
    Volume30
    Issue number1
    DOIs
    Publication statusPublished - 16 Jan 2009

    Keywords

    • Molummuno
    • Sysbio
    • Cellbio

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