CD200R1 Supports HSV-1 Viral Replication and Licenses Pro-Inflammatory Signaling Functions of TLR2
MacKay, Christopher R.
Ryan, Glennice Bowen
Cerny, Anna M.
Thompson, Mikayla R.
Kurt-Jones, Evelyn A.Note: Order does not necessarily reflect citation order of authors.
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CitationSoberman, Roy J., Christopher R. MacKay, Christine A. Vaine, Glennice Bowen Ryan, Anna M. Cerny, Mikayla R. Thompson, Boris Nikolic, et al. 2012. CD200R1 supports HSV-1 viral replication and licenses pro-inflammatory signaling functions of TLR2. PLoS ONE 7(10): e47740.
AbstractThe CD200R1:CD200 axis is traditionally considered to limit tissue inflammation by down-regulating pro-inflammatory signaling in myeloid cells bearing the receptor. We generated CD200R1−/− mice and employed them to explore both the role of CD200R1 in regulating macrophage signaling via TLR2 as well as the host response to an in vivo, TLR2-dependent model, herpes simplex virus 1 (HSV-1) infection. CD200R1−/− peritoneal macrophages demonstrated a 70–75% decrease in the generation of IL-6 and CCL5 (Rantes) in response to the TLR2 agonist Pam2CSK4 and to HSV-1. CD200R1−/− macrophages could neither up-regulate the expression of TLR2, nor assemble a functional inflammasome in response to HSV-1. CD200R1−/− mice were protected from HSV-1 infection and exhibited dysfunctional TLR2 signaling. Finally, both CD200R1−/− mice and CD200R1−/− fibroblasts and macrophages showed a markedly reduced ability to support HSV-1 replication. In summary, our data demonstrate an unanticipated and novel requirement for CD200R1 in “licensing” pro-inflammatory functions of TLR2 and in limiting viral replication that are supported by ex vivo and in vivo evidence.
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