Proteomics

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Spatiotemporal changes of the phagosomal proteome in dendritic cells in response to LPS stimulation


ABSTRACT: Dendritic cells (DCs) are professional phagocytes that use innate sensing and phagocytosis to internalize and degrade self as well as foreign material, such as pathogenic bacteria, within phagosomes. These intracellular compartments are equipped to generate antigenic peptides that serve as source for antigen presentation to T cells initiating adaptive immune responses. Nonetheless, the phagosomal proteome of DCs is only partially studied, in particular in response to inflammatory cues. The phagosomal proteome is highly dynamic as it changes during phagosome maturation, when phagosomes sequentially interact with endosomes and lysosomes. In addition, the activation status of the phagocyte can modulate the phagosomal composition and is able to shape phagosomal functions. In this study, we determined spatiotemporal changes of the proteome of DC phagosomes during their maturation and compared resting and lipopolysaccharide (LPS)-stimulated bone marrow-derived DCs by label-free, quantitative mass spectrometry. Ovalbumin-coupled latex beads were used as phagocytosis model system and revealed that LPS-treated DCs show decreased recruitment of proteins involved in phagosome maturation, such as subunits of the vacuolar proton ATPase, cathepsin B, D, S and RAB7. In contrast, those phagosomes were characterized by an increased recruitment of proteins involved in antigen cross-presentation, e.g. different subunits of the proteasome and MHC I molecules, tapasin etc., confirming increased antigen presentation efficacy in those cells. In addition, we identified several phagosomal proteins that were not previously associated with phagosomal functions and reveal a novel role for immune-responsive gene 1 (IRG1) in phagocytic uptake of particles in resting DCs.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Dendritic Cell

SUBMITTER: Matthias Trost  

LAB HEAD: Pr Matthias Trost

PROVIDER: PXD012155 | Pride | 2019-02-28

REPOSITORIES: Pride

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Publications

Spatiotemporal Changes of the Phagosomal Proteome in Dendritic Cells in Response to LPS Stimulation.

Pauwels Anne-Marie AM   Härtlova Anetta A   Peltier Julien J   Driege Yasmine Y   Baudelet Griet G   Brodin Priscille P   Trost Matthias M   Beyaert Rudi R   Hoffmann Eik E  

Molecular & cellular proteomics : MCP 20190226 5


Dendritic cells (DCs) are professional phagocytes that use innate sensing and phagocytosis to internalize and degrade self as well as foreign material, such as pathogenic bacteria, within phagosomes. These intracellular compartments are equipped to generate antigenic peptides that serve as source for antigen presentation to T cells initiating adaptive immune responses. The phagosomal proteome of DCs is only partially studied and is highly dynamic as it changes during phagosome maturation, when p  ...[more]

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