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Involvement of TLR2 in recognition of acute gammaherpesvirus-68 infection.

Publication Type:

Journal Article

Source:

PLoS One, Volume 5, Issue 10, p.e13742 (2010)

Keywords:

Animals, Cell Line, Cells, Cultured, Gammaherpesvirinae, Genes, Reporter, Herpesviridae Infections, Humans, Interferon-gamma, Interleukin-6, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Myeloid Differentiation Factor 88, NF-kappa B, Toll-Like Receptor 2

Abstract:

<p><b>BACKGROUND: </b>Toll-like receptors (TLRs) play a crucial role in the activation of innate immunity in response to many viruses. We previously reported the implication of TLR2 in the recognition of Epstein-Barr virus (EBV) by human monocytes. Because murine gammaherpesvirus-68 (MHV-68) is a useful model to study human gammaherpesvirus pathogenesis in vivo, we evaluated the importance of mouse TLR2 in the recognition of MHV-68.</p><p><b>METHODOLOGY/PRINCIPAL FINDINGS: </b>In studies using transfected HEK293 cells, MHV-68 lead to the activation of NF-κB reporter through TLR2. In addition, production of interleukin-6 (IL-6) and interferon-α (IFN-α) upon MHV-68 stimulation was reduced in murine embryonic fibroblasts (MEFs) derived from TLR2-/- and MyD88-/- mice as compared to their wild type (WT) counterpart. In transgenic mice expressing a luciferase reporter gene under the control of the mTLR2 promoter, MHV-68 challenge activated TLR2 transcription. Increased expression levels of TLR2 on blood granulocytes (CD115(-)Gr1(+)) and inflammatory monocytes (CD115(+)Gr1(+)), which mobilized to the lungs upon infection with MHV-68, was also confirmed by flow cytometry. Finally, TLR2 or MyD88 deficiency was associated with decreased IL-6 and type 1 IFN production as well as increased viral burden during short-term challenges with MHV-68.</p><p><b>CONCLUSIONS/SIGNIFICANCE: </b>TLR2 contributes to the production of inflammatory cytokines and type 1 IFN as well as to the control of viral burden during infection with MHV-68. Taken together, our results suggest that the TLR2 pathway has a relevant role in the recognition of this virus and in the subsequent activation of the innate immune response.</p>

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