Characterization and Transcriptomic Analysis of Porcine Blood Conventional and Plasmacytoid Dendritic Cells Reveals Striking Species-Specific Differences.
Porcine dendritic cells (DCs) are relatively well characterized, but a clear-cut identification of all DC subsets combined with full transcriptional profiling was lacking, preventing an unbiased insight into the functional specializations of DC subsets. Using a large panel of Abs in multicolor flow cytometry, cell sorting, and RNA sequencing we identified and characterized the porcine equivalent of conventional DCs (cDC) 1 and cDC2 as well as plasmacytoid DCs (pDCs) in the peripheral blood of pigs. We demonstrate that cDC1 are CD135+CD14-CD172alowCADM1+wCD11R1+cells, cDC2 are CD135+CD14-CD172a+CADM1+CD115+wCD11R1+CD1+cells and pDCs are CD4+CD135+CD172a+CD123+CD303+cells. As described in other species, only cDC1 express BATF3 and XCR1, cDC2 express FCER1A and FCGR2B, and only pDCs express TCF4 and NRP1 Nevertheless, despite these cross-species conserved subset-specific transcripts, porcine pDCs differed from the species described so far in many expressed genes and transcriptomic profiling clustered pDCs more distantly from cDCs than monocytes. The response of porcine DC subsets to TLR ligands revealed that pDCs are by far the most important source of TNF-α, IL-12p40, and of course IFN-α, whereas cDCs are most efficient in MHC and costimulatory molecule expression. Nevertheless, upregulation of CD40 and CD86 in cDCs was critically influenced or even dependent on the presence of pDCs, particularly for TLR 7 and 9 ligands. Our data demonstrate that extrapolation of data on DC biology from one species to another has to be done with care, and it shows how functional details have evolved differentially in different species.
Institute of Virology and Immunology, 3147 Mittelhäusern, Switzerland.
Gael
G
Auray
Interfaculty Bioinformatics Unit and Swiss Institute of Bioinformatics, University of Bern, 3012 Bern, Switzerland; and.
Irene
I
Keller
Institute of Virology and Immunology, 3147 Mittelhäusern, Switzerland.
Sylvie
S
Python
Institute of Virology and Immunology, 3147 Mittelhäusern, Switzerland.
Markus
M
Gerber
Interfaculty Bioinformatics Unit and Swiss Institute of Bioinformatics, University of Bern, 3012 Bern, Switzerland; and.
Remy
0000-0003-4733-7922
R
Bruggmann
Institute of Virology and Immunology, 3147 Mittelhäusern, Switzerland.
Nicolas
N
Ruggli
Institute of Virology and Immunology, 3147 Mittelhäusern, Switzerland; artur.summerfield@ivi.admin.ch.|Department of Infectious Diseases and Pathobiology, University of Bern, 3012 Bern, Switzerland.
Artur
0000-0001-8292-4634
A
Summerfield
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001773:Blood Cells / Q000502:physiology*; D002454:Cell Differentiation; D002469:Cell Separation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D007371:Interferon-gamma / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D013045:Species Specificity; D013552:Swine / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015703:Antigens, CD; D053762:Interleukin-12 Subunit p40; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma