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

作者：Yew Kok Hooi; Carsten Bonnie; Harrison Christopher^*

来源：Molecular Immunology, 2010, 47(4): 883-893.

DOI：10.1016/j.molimm.2009.10.009

• HCMV
• THP-1
• SR-A1
• TLR-2/-3/-9
• TNF-alpha
• IFN-beta
• IL-12p35

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-beta. NF-kappa B p65 and TNF-alpha 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-alpha and IL-12 genes is TLR-2-dependent fashion. However, induction of both TLR-3-mediated IFN-beta and TLR-9-mediated TNF-alpha 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.

• 出版日期2010-1