Varicella-zoster virus activates inflammatory cytokines in human monocytes and macrophages via Toll-like receptor 2.
The pattern recognition receptor Toll-like receptor 2 (TLR2) has been implicated in the response to several human viruses, including herpes simplex viruses (types 1 and 2) and cytomegalovirus. We demonstrated that varicella-zoster virus (VZV) activates inflammatory cytokine responses via TLR2. VZV specifically induced interleukin-6 (IL-6) in human monocytes via TLR2-dependent activation of NF-kappaB, and small interfering RNA designed to suppress TLR2 mRNA reduced the IL-6 response to VZV in human monocyte-derived macrophages. Unlike other herpesviruses, the cytokine response to VZV was species specific. VZV did not induce cytokines in murine embryonic fibroblasts or in a mouse cell line, although VZV did activate NF-kappaB in a human cell line expressing a murine TLR2 construct. Together, these results suggest that TLR2 may play a role in the inflammatory response to VZV infection.
Wang
Jennifer P
JP
Department of Medicine, University of Massachusetts Medical Center, Worcester, 01605, USA. jennifer.wang@umassmed.edu
Kurt-Jones
Evelyn A
EA
Shin
Ok S
OS
Manchak
Michael D
MD
Levin
Myron J
MJ
Finberg
Robert W
RW
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006562:Herpes Zoster / Q000276:immunology* / Q000473:pathology; D014645:Herpesvirus 3, Human / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D015850:Interleukin-6 / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology* / Q000821:virology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D009000:Monocytes / Q000276:immunology* / Q000821:virology; D016328:NF-kappa B / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology*; D013045:Species Specificity; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D015854:Up-Regulation
D016207:Cytokines; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors