High-Resolution Profiling of Innate Immune Responses by Porcine Dendritic Cell Subsetsin vitroandin vivo

The present study investigated the transcriptomic response of porcine dendritic cells (DC) to innate stimulationin vitroandin vivo. The aim was to identify DC subset-specialization, suitable Toll-like receptor (TLR) ligands targeting plasmacytoid DC (pDC), and the DC activation profile during highly and low virulent classical swine fever virus (CSFV, strain Eystrup and Pinar del Rio, respectively) infection, chosen as model for a virus causing a severe immunopathology. After identification of porcine conventional DC (cDC) 1, cDC2, pDC and a monocyte-derived subset in lymphoid tissues, we characterized DC activation using transcriptomics, and focused on chemokines, interferons, cytokines, as well as on co-stimulatory and inhibitory molecules. We demonstrate that porcine pDC provide important signals for Th1 and interferon responses, with CpG triggering the strongest responses in pDC. DC isolated early after infection of pigs with either of the two CSFV strains showed prominent upregulation ofCCL5, CXCL9, CXCL10, CXCL11, andXCL1, as well as of the cytokinesTNFSF13B, IL6, IL7, IL12B, IL15, IL27. Transcription ofIL12Band many interferon genes were mostly restricted to pDC. Interestingly, the infection was associated with a prominent induction of inhibitory and cell death receptors. When comparing low and highly virulent CSFV strains, the latter induced a stronger inflammatory and antiviral response but a weaker cell cycle response, and reduced antigen presentation functions of DC. Taken together, we provide high-resolution information on DC activation in pigs, as well as information on how DC modulation could be linked to CSFV immunopathology.