Quantitative proteomics reveals subset-specific viral recognition in dendritic cells.
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.
Luber
Christian A
CA
Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.
Cox
Jürgen
J
Lauterbach
Henning
H
Fancke
Ben
B
Selbach
Matthias
M
Tschopp
Jurg
J
Akira
Shizuo
S
Wiegand
Marian
M
Hochrein
Hubertus
H
O'Keeffe
Meredith
M
Mann
Matthias
M
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D002469:Cell Separation; D002478:Cells, Cultured; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D040901:Proteomics / Q000295:instrumentation / Q000379:methods*; D010253:Respirovirus Infections / Q000276:immunology*; D029082:Sendai virus / Q000276:immunology* / Q000472:pathogenicity
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D053594:Myeloid Differentiation Factor 88; C512612:MAVS protein, mouse; C507780:Myd88 protein, mouse; C503356:Ddx58 protein, mouse