Journal
MOLECULAR & CELLULAR PROTEOMICS
Volume 14, Issue 5, Pages 1334-1349Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/mcp.M114.044594
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Funding
- Wellcome Trust [097945/Z/11/Z, 081867/Z/06/Z]
- Medical Research Council UK
- AstraZeneca
- Boehringer-Ingelheim
- GlaxoSmithKline
- Janssen Pharmaceutica
- Merck KGaA
- Pfizer
- Medical Research Council [G1100713, MC_UU_12016/5, MC_UP_A500_1020] Funding Source: researchfish
- MRC [MC_UU_12016/5, G1100713, MC_UP_A500_1020] Funding Source: UKRI
- Wellcome Trust [081867/Z/06/Z] Funding Source: Wellcome Trust
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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-B 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.
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