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


RESULTS
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
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.
Laboratory of Innate Immunology, Centre Hospitalier Universitaire de Québec Research Center and Department of Molecular Medicine, Faculty of Medicine, Université Laval, Quebec, Canada.
François
F
Michaud
François
F
Coulombe
Eric
E
Gaudreault
Jasna
J
Kriz
Jean
J
Gosselin
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D018142:Gammaherpesvirinae / Q000302:isolation & purification / Q000502:physiology*; D017930:Genes, Reporter; D006566:Herpesviridae Infections / Q000503:physiopathology* / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000502:physiology*
D015850:Interleukin-6; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D051195:Toll-Like Receptor 2; D007371:Interferon-gamma