Dissecting the molecular programs governing interferon production by plasmacytoid dendritic cells during a viral infection in vivo

Plasmacytoid dendritic cells (pDC) are the major source of type I and type III interferons (IFN-I/III) during viral infections, in response to triggering of endosomal Toll Like Receptors (TLRs) 7 or 9 by viral single-stranded RNA or unmethylated CpG DNA, respectively. Interestingly, this function is restricted to a minor fraction of pDC (Zucchini et al. Int. Immunol. 2008). In this project, we aimed at identifying the molecular pathways involved in inducing IFN-I/III production in this minor faction of pDC during in vivo infection by the mouse cytomegalovirus (MCMV). To achive this goal, we infected with MCMV Ifnb1Eyfp mice, in which IFN-producing pDC can be detected by YFP expression (Scheu et al. PNAS 2008). Thanks to this model, we were able to sort three distinct subsets of pDC: CD86-YFP- (not activated, non IFN-producing), CD86+YFP- (activated, non IFN-producing) and CD86+YFP+ (activated, IFN-producing) and to perform microarray analysis. This allowed us to select genes differentially expressed among these three subsets and to mine these data in order to identify the related signaling pathways.

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Abbas A, Vu Manh TP, Valente M, Collinet N, Attaf N, Dong C, Naciri K, Chelbi R, Brelurut G, Cervera-Marzal I, Rauwel B, Davignon JL, Bessou G, Thomas-Chollier M, Thieffry D, Villani AC, Milpied P, Dalod M, Tomasello E