Human herpesvirus 6 infection impairs Toll-like receptor signaling.
Human herpesvirus 6 (HHV-6) has a tropism for immunocompetent cells, including T lymphocytes, monocytes/macrophages, and dendritic cells (DCs) suggesting that HHV-6 infection affects the immunosurveillance system. Toll-like receptor (TLR) system plays an important role in innate immunity against various pathogens. In the present study, we investigated the effect of HHV-6 infection on the expression and intracellular signaling of TLRs in DCs. Although expression levels of TLRs were not decreased or slightly elevated following HHV-6 infection, the amounts of cytokines produced following stimulation with ligands for TLRs appeared to be dramatically decreased in HHV-6-infected DCs as compared to mock-infected DCs. Similarly, phosphorylation levels of TAK-1, IkappaB kinase, and IkappaB-alpha following stimulation of HHV-6-infected DCs with lipopolysaccharide, which is the ligand for TLR4, appeared to be decreased. These data show that HHV-6 impairs intracellular signaling through TLRs indicating the novel mechanism of HHV-6-mediated immunomodulation.
Murakami
Yuichi
Y
Departmemt of Bioregulatory Medicine, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Tanimoto
Kazushi
K
Fujiwara
Hiroshi
H
An
Jun
J
Suemori
Koichiro
K
Ochi
Toshiki
T
Hasegawa
Hitoshi
H
Yasukawa
Masaki
M
D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000821:virology*; D020869:Gene Expression Profiling; D015654:Herpesvirus 6, Human / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000276:immunology*
D016207:Cytokines; D051193:Toll-Like Receptors
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