Quantitative Proteomics Reveals Subset-Specific Viral Recognition in Dendritic Cells

Immunity. 2010 Feb 26;32(2):279-89. doi: 10.1016/j.immuni.2010.01.013. Epub 2010 Feb 18.

Abstract

Dendritic cell (DC) populations consist of multiple subsets that are essential orchestrators of the immune system. Technological limitations have so far prevented systems-wide accurate proteome comparison of rare cell populations in vivo. Here, we used high-resolution mass spectrometry-based proteomics, combined with label-free quantitation algorithms, to determine the proteome of mouse splenic conventional and plasmacytoid DC subsets to a depth of 5,780 and 6,664 proteins, respectively. We found mutually exclusive expression of pattern recognition pathways not previously known to be different among conventional DC subsets. Our experiments assigned key viral recognition functions to be exclusively expressed in CD4(+) and double-negative DCs. The CD8alpha(+) DCs largely lack the receptors required to sense certain viruses in the cytoplasm. By avoiding activation via cytoplasmic receptors, including retinoic acid-inducible gene I, CD8alpha(+) DCs likely gain a window of opportunity to process and present viral antigens before activation-induced shutdown of antigen presentation pathways occurs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Antigens, CD / biosynthesis
  • Antigens, CD / genetics
  • Cell Separation
  • Cells, Cultured
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / biosynthesis*
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / immunology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Dendritic Cells / pathology
  • Dendritic Cells / virology
  • Flow Cytometry
  • Host-Pathogen Interactions
  • Mass Spectrometry
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / metabolism
  • Proteomics / instrumentation
  • Proteomics / methods*
  • Respirovirus Infections / immunology*
  • Sendai virus / immunology*
  • Sendai virus / pathogenicity

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, CD
  • IPS-1 protein, mouse
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Ddx58 protein, mouse
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases