HHV-6B induces IFN-lambda1 responses in cord plasmacytoid dendritic cells through TLR9.
Human herpesvirus type 6B (HHV-6B) is a strong inducer of IFN-alpha and has the capacity to promote Th1 responses and block Th2 responses in vitro. In this study we addressed whether inactivated HHV-6B can also induce IFN lambda responses and to what extent interferons alpha and lambda affect Th1/Th...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3368904?pdf=render |
| _version_ | 1811232098452766720 |
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| author | Inger Nordström Kristina Eriksson |
| author_facet | Inger Nordström Kristina Eriksson |
| author_sort | Inger Nordström |
| collection | DOAJ |
| description | Human herpesvirus type 6B (HHV-6B) is a strong inducer of IFN-alpha and has the capacity to promote Th1 responses and block Th2 responses in vitro. In this study we addressed whether inactivated HHV-6B can also induce IFN lambda responses and to what extent interferons alpha and lambda affect Th1/Th2 polarization. We show that inactivated HHV-6B induced IFN-lambda1 (IL-29) but not IFN-lambda2 (IL-28A) responses in plasmacytoid DC and that this induction was mediated through TLR9. We have previously shown that HHV-6B promotes Th1 responses and blocks Th2 responses in both humans and mice. We now show that neutralization of IFN-alpha but not IFN-lambda1 blocked the HHV-6B-induced enhancement of Th1 responses in MLR, but did not affect the HHV-6-induced dampening of Th2 responses. Similarly, blockage of TLR9 counteracted HHV-6Bs effects on the Th1/Th2 balance. In addition, IFN-alpha but not IFN-lambda1 promoted IFN-gamma production and blocked IL-5 and IL-13 production in purified CD4+ T-cells. The lack of effect of IFN-lambda1 correlated with the absence of the IFN-lambda receptor IL-28Ralfa chain on the cell surface of both resting and activated CD4+ T-cells. We conclude that inactivated HHV-6B is a strong inducer of IFN-lambda1 in plasmacytoid DC and that this induction is TLR9-dependent. However, human CD4+ T-cells do not express the IFN-lambda receptor and are refractory to IFN-lambda1 treatment. The HHV-6B-induced alterations in the Th1/Th2 balance are instead mediated mainly through TLR9 and IFN-alpha. |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T10:56:32Z |
| publishDate | 2012-01-01 |
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| series | PLoS ONE |
| spelling | doaj.art-4020ab14f6344b0aba20269c750d3df72022-12-22T03:36:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0176e3868310.1371/journal.pone.0038683HHV-6B induces IFN-lambda1 responses in cord plasmacytoid dendritic cells through TLR9.Inger NordströmKristina ErikssonHuman herpesvirus type 6B (HHV-6B) is a strong inducer of IFN-alpha and has the capacity to promote Th1 responses and block Th2 responses in vitro. In this study we addressed whether inactivated HHV-6B can also induce IFN lambda responses and to what extent interferons alpha and lambda affect Th1/Th2 polarization. We show that inactivated HHV-6B induced IFN-lambda1 (IL-29) but not IFN-lambda2 (IL-28A) responses in plasmacytoid DC and that this induction was mediated through TLR9. We have previously shown that HHV-6B promotes Th1 responses and blocks Th2 responses in both humans and mice. We now show that neutralization of IFN-alpha but not IFN-lambda1 blocked the HHV-6B-induced enhancement of Th1 responses in MLR, but did not affect the HHV-6-induced dampening of Th2 responses. Similarly, blockage of TLR9 counteracted HHV-6Bs effects on the Th1/Th2 balance. In addition, IFN-alpha but not IFN-lambda1 promoted IFN-gamma production and blocked IL-5 and IL-13 production in purified CD4+ T-cells. The lack of effect of IFN-lambda1 correlated with the absence of the IFN-lambda receptor IL-28Ralfa chain on the cell surface of both resting and activated CD4+ T-cells. We conclude that inactivated HHV-6B is a strong inducer of IFN-lambda1 in plasmacytoid DC and that this induction is TLR9-dependent. However, human CD4+ T-cells do not express the IFN-lambda receptor and are refractory to IFN-lambda1 treatment. The HHV-6B-induced alterations in the Th1/Th2 balance are instead mediated mainly through TLR9 and IFN-alpha.http://europepmc.org/articles/PMC3368904?pdf=render |
| spellingShingle | Inger Nordström Kristina Eriksson HHV-6B induces IFN-lambda1 responses in cord plasmacytoid dendritic cells through TLR9. PLoS ONE |
| title | HHV-6B induces IFN-lambda1 responses in cord plasmacytoid dendritic cells through TLR9. |
| title_full | HHV-6B induces IFN-lambda1 responses in cord plasmacytoid dendritic cells through TLR9. |
| title_fullStr | HHV-6B induces IFN-lambda1 responses in cord plasmacytoid dendritic cells through TLR9. |
| title_full_unstemmed | HHV-6B induces IFN-lambda1 responses in cord plasmacytoid dendritic cells through TLR9. |
| title_short | HHV-6B induces IFN-lambda1 responses in cord plasmacytoid dendritic cells through TLR9. |
| title_sort | hhv 6b induces ifn lambda1 responses in cord plasmacytoid dendritic cells through tlr9 |
| url | http://europepmc.org/articles/PMC3368904?pdf=render |
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