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

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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. The phagosomal proteome of DCs is only partially studied and 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 MHC I molecules, the proteasome and tapasin, confirming the observed increase in cross-presentation efficacy in those cells. Further, several proteins were identified that were not previously associated with phagosomal functions. Hierarchical clustering of phagosomal proteins demonstrated that their acquisition to DC phagosomes is not only dependent on the duration of phagosome maturation but also on the activation state of DCs. Thus, our study provides a comprehensive overview of how DCs alter their phagosome composition in response to LPS, which has profound impact on the initiation of efficient immune responses.
Keywords
SYSTEMS BIOLOGY ANALYSIS, CROSS-PRESENTATION, HOOK3 PROTEIN, CUTTING, EDGE, MATURATION, ANTIGEN, FUSION, GENE, NF-KAPPA-B2, BINDING

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Chicago
Pauwels, Anne-Marie, Anetta Hartlova, Julien Peltier, Yasmine Driege, Griet Baudelet, Priscille Brodin, Matthias Trost, Rudi Beyaert, and Eik Hoffmann. 2019. “Spatiotemporal Changes of the Phagosomal Proteome in Dendritic Cells in Response to LPS Stimulation.” Molecular & Cellular Proteomics 18 (5): 909–922.
APA
Pauwels, A.-M., Hartlova, A., Peltier, J., Driege, Y., Baudelet, G., Brodin, P., Trost, M., et al. (2019). Spatiotemporal changes of the phagosomal proteome in dendritic cells in response to LPS stimulation. MOLECULAR & CELLULAR PROTEOMICS, 18(5), 909–922.
Vancouver
1.
Pauwels A-M, Hartlova A, Peltier J, Driege Y, Baudelet G, Brodin P, et al. Spatiotemporal changes of the phagosomal proteome in dendritic cells in response to LPS stimulation. MOLECULAR & CELLULAR PROTEOMICS. 2019;18(5):909–22.
MLA
Pauwels, Anne-Marie et al. “Spatiotemporal Changes of the Phagosomal Proteome in Dendritic Cells in Response to LPS Stimulation.” MOLECULAR & CELLULAR PROTEOMICS 18.5 (2019): 909–922. Print.
@article{8617542,
  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. The phagosomal proteome of DCs is only partially studied and 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 MHC I molecules, the proteasome and tapasin, confirming the observed increase in cross-presentation efficacy in those cells. Further, several proteins were identified that were not previously associated with phagosomal functions. Hierarchical clustering of phagosomal proteins demonstrated that their acquisition to DC phagosomes is not only dependent on the duration of phagosome maturation but also on the activation state of DCs. Thus, our study provides a comprehensive overview of how DCs alter their phagosome composition in response to LPS, which has profound impact on the initiation of efficient immune responses.},
  author       = {Pauwels, Anne-Marie and Hartlova, Anetta and Peltier, Julien and Driege, Yasmine and Baudelet, Griet and Brodin, Priscille and Trost, Matthias and Beyaert, Rudi and Hoffmann, Eik},
  issn         = {1535-9476},
  journal      = {MOLECULAR & CELLULAR PROTEOMICS},
  keywords     = {SYSTEMS BIOLOGY ANALYSIS,CROSS-PRESENTATION,HOOK3 PROTEIN,CUTTING,EDGE,MATURATION,ANTIGEN,FUSION,GENE,NF-KAPPA-B2,BINDING},
  language     = {eng},
  number       = {5},
  pages        = {909--922},
  title        = {Spatiotemporal changes of the phagosomal proteome in dendritic cells in response to LPS stimulation},
  url          = {http://dx.doi.org/10.1074/mcp.RA119.001316},
  volume       = {18},
  year         = {2019},
}

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