Scavenger receptor A1 is required for sensing HCMV by endosomal TLR-3/-9 in monocytic THP-1 cells

Monocytes provide initial surveillance for pathogenic glycopeptides via scavenger receptors (SRs) and for viruses via Toll-like receptors (TLRs) which trigger pro-inflammatory response. However, specific interactions between SR-A1 and TLRs have not yet been assessed in human cytomegalovirus (HCMV)-exposed monocytes. Our results showed two patterns of gene expression upon HCMV exposure: genes that were induced within 10 min include SR-A1, Lyn, TLR-2, and IL-12p35, whereas those induced at 1 h are TLR-3, TLR-9, TRIF, IRF-3, and IFN-β. NF-κB p65 and TNF-α were elevated at both 10 min and 1 h post exposure. Further, inhibitory studies using neutralizing antibodies and morpholino antisense oligonucleotides suggested that within 10 min of HCMV exposure, transcription of TNF-α and IL-12 genes is TLR-2-dependent fashion. However, induction of both TLR-3-mediated IFN-β and TLR-9-mediated TNF-α at 1 h was dependent on SR-A1. These findings reveal a novel mechanistic insight into an interrelationship between SR-A1 and TLR-3/-9 signaling in HCMV-exposed monocytes.