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* Virologie et Immunologie Moléculaires, UR892 Institut National de la Recherche Agronomique, Jouy-en-Josas;
Centre de Recherche en Imagerie Interventionnelle, Jouy-en-Josas, France;
Plateau d’instrumentation et de compétences en transcriptomique, Jouy-en-Josas, France;
Plate-forme de cytométrie, Institut Pasteur, Paris, France;
¶ Interactions hôte-pathogènes, École Nationale Vétérinaire de Toulouse-Institut National de la Recherche Agronomique, Toulouse, France;
|| Institute of Virology and Immunoprophylaxis, Mittelhausern, Switzerland; and
# Institute for Animal Health, Compton, United Kingdom
Conventional dendritic cells enter lymph nodes by migrating from peripheral tissues via the lymphatic route, whereas plasmacytoid dendritic cells (pDC), also called IFN-producing cells (IPC), are described to gain nodes from blood via the high endothelial venules. We demonstrate here that IPC/pDC migrate in the afferent lymph of two large mammals. In sheep, injection of type A CpG oligodinucleotide (ODN) induced lymph cells to produce type I IFN. Furthermore, low-density lymph cells collected at steady state produced type I IFN after stimulation with type A CpG ODN and enveloped viruses. Sheep lymph IPC were found within a minor BnegCD11cneg subset expressing CD45RB. They presented a plasmacytoid morphology, expressed high levels of TLR-7, TLR-9, and IFN regulatory factor 7 mRNA, induced IFN-
production in allogeneic CD4pos T cells, and differentiated into dendritic cell-like cells under viral stimulation, thus fulfilling criteria of bona fide pDC. In mini-pig, a CD4posSIRPpos subset in afferent lymph cells, corresponding to pDC homologs, produced type I IFN after type A CpG-ODN triggering. Thus, pDC can link innate and acquired immunity by migrating from tissue to draining node via lymph, similarly to conventional dendritic cells.
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1 F.P. performed the largest part of research, analyzed data, and prepared figures. V.C. performed research, analyzed data, prepared figures, and wrote small sections. M.B. performed surgery. A.C. performed initial research. S.C., C.B., N.B., and A.-M.B. contributed to analytical tools. M.E., V.N., J.H., E.F., B.R., L.G.-P., and S.R. provided critical reagents. B.C. designed initial research, analyzed data, and supervised experiments. I.S.-C. designed research, analyzed data, supervised experiments, and drafted the manuscript and figures.
2 B.C. and I.S.-C. share senior authorship.
3 Address correspondence and reprint requests to Dr. Isabelle Schwartz-Cornil, Unité de Virologie et Immunologie Moléculaires, UR892 Institut National de la Recherche Agronomique, Domaine de Vilvert, 78352 Jouy-en-Josas Cedex, France. E-mail address: isabelle.schwartz{at}jouy.inra.fr
4 Abbreviations used in this paper: DC, dendritic cell; TL, total lymph; LDL, low-density lymph; IPC, IFN-producing cells; ODN, oligodinucleotide; UV-TGEV, UV-irradiated transmissible gastroenteritis virus; cDC, conventional DC; pDC, plasmacytoid DC; GAM, goat anti-mouse; CT, cycle threshold.
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