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

Abstract

BACKGROUND:

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.

METHODOLOGY/PRINCIPAL FINDINGS:

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.

CONCLUSIONS/SIGNIFICANCE:

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.

• Authors: François Michaud, François Coulombe, Eric Gaudreault, Jasna Kriz, Jean Gosselin
• Journal: PloS one (PLoS One) Vol. 5 Issue 10 Pg. e13742 (Oct 29 2010) ISSN: 1932-6203 [Electronic] United States
• PMID: 21060793 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-6
• MYD88 protein, human
• Myeloid Differentiation Factor 88
• NF-kappa B
• Toll-Like Receptor 2
• Interferon-gamma

Topics

• Animals
• Cell Line
• Cells, Cultured
• Gammaherpesvirinae (isolation & purification, physiology)
• Genes, Reporter
• Herpesviridae Infections (physiopathology, virology)
• Humans
• Interferon-gamma (biosynthesis)
• Interleukin-6 (biosynthesis)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• Myeloid Differentiation Factor 88 (metabolism)
• NF-kappa B (metabolism)
• Toll-Like Receptor 2 (genetics, physiology)