Publication date: Sep 25, 2023
Plasmacytoid dendritic cells (pDCs) are a rare subset of dendritic cells that exhibit antiviral functions in response to toll-like receptor (TLR) 7/8 stimulations. Alternative TLRs such as TLR4 have been known to be active in pDCs for immune regulatory functions. However, it is unclear whether these TLRs differentially activate pDCs as compared with canonical TLR7/8 stimulation. Here, we assessed alternative pDC activation states mediated by TLRs other than endosomal TLRs via RNA sequencing approach. We found that TLR4 stimulation induced a high degree of similarity in gene expression pattern to TLR7/8 stimulation in pDCs. Despite high resemblance to TLR7/8, we discovered unique genes that were activated under TLR4 activation only as well as genes that were induced at a higher magnitude in comparison to TLR7/8 activation. In comparison between TLR4 activated pDCs and conventional dendritic cells (cDCs), we revealed that pDCs and cDCs expressed distinct gene sets, whereby cDCs mostly favored antigen presentation functions for adaptive immune response regulation while pDCs leaned towards immune response against infectious diseases. Lastly, we determined that TLR4 activation sensitized pDCs against SARS-CoV-2 (COVID-19) ssRNA by enhancing antiviral related responses and type I interferons (IFNs) production. These findings provided greater insights into TLR4 activation state in pDCs, which can be beneficial for alternative therapeutic interventions involving pDCs for various diseases.
|disease||IDO||adaptive immune response|