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Originally published In Press as doi:10.1074/mcp.M700267-MCP200 on December 21, 2007.
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Molecular & Cellular Proteomics 7:697-715, 2008.
© 2008 by The American Society for Biochemistry and Molecular Biology, Inc.

Special Issue: 8th International Symposium On Mass Spectrometry In The Life Sciences

Modulation of the Phagosome Proteome by Interferon-{gamma}*,S

Isabelle Jutras{ddagger}, Mathieu Houde{ddagger}, Nathan Currier§, Jonathan Boulais{ddagger}, Sophie Duclos{ddagger}, Sylvie LaBoissière§, Eric Bonneil§,¶, Paul Kearney§, Pierre Thibault§,¶, Eustache Paramithiotis§, Patrice Hugo§ and Michel Desjardins{ddagger},§,||

From the {ddagger} Département de pathologie et biologie cellulaire, Université de Montréal, 2900 Édouard-Montpetit, Montréal, Québec H3T 1J4, Canada and § Caprion Proteomics, 7150 Alexander-Fleming, Montréal, Québec H4S 2C8, Canada

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.

|| To whom correspondence should be addressed: Dépt. de pathologie et biologie cellulaire, Université de Montréal, 2900 Edouard-Montpetit, Montréal, Québec H3T 1J4, Canada. Tel.: 514-343-7250; Fax: 514-343-2569, E-mail: michel.desjardins{at}umontreal.ca


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