Viral infection alters mRNA expression of nuclear hormone receptors (NRs) and their coregulators in mouse dendritic cells (DCs) (131.1)

Abstract

Abstract DCs, versatile regulators of host immune response against viral infection, capture antigens and present them to T-cells and subsequently activate both innate and acquired immunity. NRs, on the other hand, are intracellular receptors which function as hormone-dependent transcription factors. Some of the NRs, such as the glucocorticoid receptor and the peroxisome proliferators-activated receptors (PPARs), suppress inflammatory reactions. Thus, we examined with real-time PCR using our custom NR PCR arrays for the mRNA expression of all mice NRs and their coregulators in bone marrow derived DCs (BMDCs) infected with viruses. At the baseline, BMDCs expressed 21 NRs. PPARγ, thyroid hormone receptor-α, retinoid X receptor-α, NGF-induced factor B and Nur related factor 1 were significantly down-regulated by virus infection (15-, 6-, 6-, 50- and 15-fold reduction, respectively), while liver X receptor-α and neuron-derived orphan receptor-1 were strongly upregulated (6- and 20-fold induction, respectively). All coregulators were expressed in BMDCs at the baseline, whereas histone deacetylase 4, 6 and 10, nuclear receptor corepressor-1 and Set-TAF-Iβ were significantly down-regulated by viruses (10-, 4-, 12-, 4- and 2-fold reduction, respectively). These results indicate that viral infection alters mRNA, and possibly, protein expression of some NRs and their coregulators. Our results suggest that NR signaling pathways are integral components of the global response of DCs to viral infection.