Limits...
Human herpesvirus 6 infection impairs Toll-like receptor signaling.

Murakami Y, Tanimoto K, Fujiwara H, An J, Suemori K, Ochi T, Hasegawa H, Yasukawa M - Virol. J. (2010)

Bottom Line: Toll-like receptor (TLR) system plays an important role in innate immunity against various pathogens.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.These data show that HHV-6 impairs intracellular signaling through TLRs indicating the novel mechanism of HHV-6-mediated immunomodulation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Departmemt of Bioregulatory Medicine, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.

ABSTRACT
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.

Show MeSH

Related in: MedlinePlus

Impairment of TLR4 signaling in HHV-6-infected DCs. (A) Western blotting reveals that the expression level of TLR4 protein in HHV-6-infected DCs, which were not stimulated with LPS, is slightly higher than that in mock-infected DCs. (B) Flow cytometric analysis using fluorescent LPS conjugate reveals that the amount of LPS bound to HHV-6-infected DCs is slightly higher than that on mock-infected DCs, suggesting that the expression level of TLR4 molecules on DCs is increased after infection with HHV-6. (C) Western blotting reveals that the expression levels of MyD88 and TRAF6 proteins in HHV-6-infected DCs, which are not stimulated with LPS, are slightly higher than those in mock-infected DCs. (D) Western blotting reveals that phosphorylation levels of TAK-1, IKKα/β and IκB-α in HHV-6-infected DCs after stimulation with LPS are significantly lower than those in LPS-stimulated mock-infected DCs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2874541&req=5

Figure 3: Impairment of TLR4 signaling in HHV-6-infected DCs. (A) Western blotting reveals that the expression level of TLR4 protein in HHV-6-infected DCs, which were not stimulated with LPS, is slightly higher than that in mock-infected DCs. (B) Flow cytometric analysis using fluorescent LPS conjugate reveals that the amount of LPS bound to HHV-6-infected DCs is slightly higher than that on mock-infected DCs, suggesting that the expression level of TLR4 molecules on DCs is increased after infection with HHV-6. (C) Western blotting reveals that the expression levels of MyD88 and TRAF6 proteins in HHV-6-infected DCs, which are not stimulated with LPS, are slightly higher than those in mock-infected DCs. (D) Western blotting reveals that phosphorylation levels of TAK-1, IKKα/β and IκB-α in HHV-6-infected DCs after stimulation with LPS are significantly lower than those in LPS-stimulated mock-infected DCs.

Mentions: We further examined the mechanisms of impaired cytokine production by HHV-6-infected DCs, focusing on TLR4. First, expression of the TLR4 molecule on HHV-6-infected and mock-infected DCs was examined by Western blotting of cell lysates and flow cytometry to detect the binding of fluorescent LPS conjugate. As shown in Figures 3A and 3B, the level of TLR4 expression on HHV-6-infected DCs unstimulated with LPS appeared to be slightly higher than that on mock-infected DCs.


Human herpesvirus 6 infection impairs Toll-like receptor signaling.

Murakami Y, Tanimoto K, Fujiwara H, An J, Suemori K, Ochi T, Hasegawa H, Yasukawa M - Virol. J. (2010)

Impairment of TLR4 signaling in HHV-6-infected DCs. (A) Western blotting reveals that the expression level of TLR4 protein in HHV-6-infected DCs, which were not stimulated with LPS, is slightly higher than that in mock-infected DCs. (B) Flow cytometric analysis using fluorescent LPS conjugate reveals that the amount of LPS bound to HHV-6-infected DCs is slightly higher than that on mock-infected DCs, suggesting that the expression level of TLR4 molecules on DCs is increased after infection with HHV-6. (C) Western blotting reveals that the expression levels of MyD88 and TRAF6 proteins in HHV-6-infected DCs, which are not stimulated with LPS, are slightly higher than those in mock-infected DCs. (D) Western blotting reveals that phosphorylation levels of TAK-1, IKKα/β and IκB-α in HHV-6-infected DCs after stimulation with LPS are significantly lower than those in LPS-stimulated mock-infected DCs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2874541&req=5

Figure 3: Impairment of TLR4 signaling in HHV-6-infected DCs. (A) Western blotting reveals that the expression level of TLR4 protein in HHV-6-infected DCs, which were not stimulated with LPS, is slightly higher than that in mock-infected DCs. (B) Flow cytometric analysis using fluorescent LPS conjugate reveals that the amount of LPS bound to HHV-6-infected DCs is slightly higher than that on mock-infected DCs, suggesting that the expression level of TLR4 molecules on DCs is increased after infection with HHV-6. (C) Western blotting reveals that the expression levels of MyD88 and TRAF6 proteins in HHV-6-infected DCs, which are not stimulated with LPS, are slightly higher than those in mock-infected DCs. (D) Western blotting reveals that phosphorylation levels of TAK-1, IKKα/β and IκB-α in HHV-6-infected DCs after stimulation with LPS are significantly lower than those in LPS-stimulated mock-infected DCs.
Mentions: We further examined the mechanisms of impaired cytokine production by HHV-6-infected DCs, focusing on TLR4. First, expression of the TLR4 molecule on HHV-6-infected and mock-infected DCs was examined by Western blotting of cell lysates and flow cytometry to detect the binding of fluorescent LPS conjugate. As shown in Figures 3A and 3B, the level of TLR4 expression on HHV-6-infected DCs unstimulated with LPS appeared to be slightly higher than that on mock-infected DCs.

Bottom Line: Toll-like receptor (TLR) system plays an important role in innate immunity against various pathogens.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.These data show that HHV-6 impairs intracellular signaling through TLRs indicating the novel mechanism of HHV-6-mediated immunomodulation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Departmemt of Bioregulatory Medicine, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus