Scavenger receptor SREC-I promotes double stranded RNA-mediated TLR3 activation in human monocytes

作者：Murshid Ayesha; Gong Jianlin; Ahmad Ridwan; Borges Thiago J; Calderwood Stuart K^*

来源：Immunobiology, 2015, 220(6): 823-832.

DOI：10.1016/j.imbio.2014.12.011

• TLR3
• SREC-I
• THP1
• Poly I:C
• Double stranded RNA
• Cytokines

Scavenger receptor associated with endothelial cells (SREC-I) was previously shown to be expressed by immune cells and to play a role in CD8(+)-mediated T cell immunity. SREC-I was also shown to modulate the function of Toll like receptors with essential roles in innate immunity. Here we have shown that SREC-I enhanced double stranded RNA (dsRNA)-mediated Toll like receptor-3 (TLR3) activation. Viral double stranded RNA (dsRNA) was demonstrated to be a pathogen associated molecular pattern (PAMP) signaling viral infection. We found that in human monocyte/macrophage THP1 cells as well as murine bone marrow derived macrophages SREC-I led to elevated responses to the dsRNA-like molecule polyinosine-polycytidylic acid (Poly I:C) and enhanced production of inflammatory cytokines. Our data also showed that intracellular/endocytic TLR3 could directly interact with SREC-I in the presence of Poly I:C. The internalized ligand, along with TLR3 and SREC-I localized in endosomes within macrophages and in HEK293 cells engineered to express TLR3 and SREC-I. SREC-I also stimulated dsRNA-mediated TLR3 activation of signaling through the NF kappa beta, MAP kinase and interferon regulatory factor 3 (IRF3) pathways leading to expression of cytokines, most notably interleukin-8 and interferon-beta. We therefore hypothesized that SREC-I could be a receptor capable of internalizing Poly I:C, boosting TLR3 mediated inflammatory signaling and stimulating cytokine production in macrophages.

• 出版日期2015-6