Quantitative Proteome Analysis of Temporally Resolved Phagosomes Following Uptake Via Key Phagocytic Receptors*

Macrophages operate at the forefront of innate immunity and their discrimination of foreign versus “self” particles is critical for a number of responses including efficient pathogen killing, antigen presentation, and cytokine induction. In order to efficiently destroy the particles and detect poten...

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Main Authors: Dill, Brian D., Gierlinski, Marek, Härtlova, Anetta, Arandilla, Alba González, Guo, Manman, Clarke, Rosemary G., Trost, Matthias
Format: Online
Language:English
Published: The American Society for Biochemistry and Molecular Biology 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4424403/
id pubmed-4424403
recordtype oai_dc
spelling pubmed-44244032015-05-18 Quantitative Proteome Analysis of Temporally Resolved Phagosomes Following Uptake Via Key Phagocytic Receptors* Dill, Brian D. Gierlinski, Marek Härtlova, Anetta Arandilla, Alba González Guo, Manman Clarke, Rosemary G. Trost, Matthias Research Macrophages operate at the forefront of innate immunity and their discrimination of foreign versus “self” particles is critical for a number of responses including efficient pathogen killing, antigen presentation, and cytokine induction. In order to efficiently destroy the particles and detect potential threats, macrophages express an array of receptors to sense and phagocytose prey particles. In this study, we accurately quantified a proteomic time-course of isolated phagosomes from murine bone marrow-derived macrophages induced by particles conjugated to seven different ligands representing pathogen-associated molecular patterns, immune opsonins or apoptotic cell markers. We identified a clear functional differentiation over the three timepoints and detected subtle differences between certain ligand-phagosomes, indicating that triggering of receptors through a single ligand type has mild, but distinct, effects on phagosome proteome and function. Moreover, our data shows that uptake of phosphatidylserine-coated beads induces an active repression of NF-κB immune responses upon Toll-like receptor (TLR)-activation by recruitment of anti-inflammatory regulators to the phagosome. This data shows for the first time a systematic time-course analysis of bone marrow-derived macrophages phagosomes and how phagosome fate is regulated by the receptors triggered for phagocytosis. The American Society for Biochemistry and Molecular Biology 2015-05 /pmc/articles/PMC4424403/ /pubmed/25755298 http://dx.doi.org/10.1074/mcp.M114.044594 Text en © 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version free via Creative Commons CC-BY license (http://creativecommons.org/licenses/by/3.0) .
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Dill, Brian D.
Gierlinski, Marek
Härtlova, Anetta
Arandilla, Alba González
Guo, Manman
Clarke, Rosemary G.
Trost, Matthias
spellingShingle Dill, Brian D.
Gierlinski, Marek
Härtlova, Anetta
Arandilla, Alba González
Guo, Manman
Clarke, Rosemary G.
Trost, Matthias
Quantitative Proteome Analysis of Temporally Resolved Phagosomes Following Uptake Via Key Phagocytic Receptors*
author_facet Dill, Brian D.
Gierlinski, Marek
Härtlova, Anetta
Arandilla, Alba González
Guo, Manman
Clarke, Rosemary G.
Trost, Matthias
author_sort Dill, Brian D.
title Quantitative Proteome Analysis of Temporally Resolved Phagosomes Following Uptake Via Key Phagocytic Receptors*
title_short Quantitative Proteome Analysis of Temporally Resolved Phagosomes Following Uptake Via Key Phagocytic Receptors*
title_full Quantitative Proteome Analysis of Temporally Resolved Phagosomes Following Uptake Via Key Phagocytic Receptors*
title_fullStr Quantitative Proteome Analysis of Temporally Resolved Phagosomes Following Uptake Via Key Phagocytic Receptors*
title_full_unstemmed Quantitative Proteome Analysis of Temporally Resolved Phagosomes Following Uptake Via Key Phagocytic Receptors*
title_sort quantitative proteome analysis of temporally resolved phagosomes following uptake via key phagocytic receptors*
description Macrophages operate at the forefront of innate immunity and their discrimination of foreign versus “self” particles is critical for a number of responses including efficient pathogen killing, antigen presentation, and cytokine induction. In order to efficiently destroy the particles and detect potential threats, macrophages express an array of receptors to sense and phagocytose prey particles. In this study, we accurately quantified a proteomic time-course of isolated phagosomes from murine bone marrow-derived macrophages induced by particles conjugated to seven different ligands representing pathogen-associated molecular patterns, immune opsonins or apoptotic cell markers. We identified a clear functional differentiation over the three timepoints and detected subtle differences between certain ligand-phagosomes, indicating that triggering of receptors through a single ligand type has mild, but distinct, effects on phagosome proteome and function. Moreover, our data shows that uptake of phosphatidylserine-coated beads induces an active repression of NF-κB immune responses upon Toll-like receptor (TLR)-activation by recruitment of anti-inflammatory regulators to the phagosome. This data shows for the first time a systematic time-course analysis of bone marrow-derived macrophages phagosomes and how phagosome fate is regulated by the receptors triggered for phagocytosis.
publisher The American Society for Biochemistry and Molecular Biology
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4424403/
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