CD200R1 supports HSV-1 viral replication and licenses pro-inflammatory signaling functions of TLR2
Soberman, Roy J. ; MacKay, Christopher R. ; Vaine, Christine A. ; Ryan, Glennice Bowen ; Cerny, Anna M. ; Thompson, Mikayla R. ; Nikolic, Boris ; Primo, Valeria ; Christmas, Peter ; Sheiffele, Paul ... show 3 more
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Abstract
The 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 Pam(2)CSK(4) 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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Soberman RJ, MacKay CR, Vaine CA, Ryan GB, Cerny AM, et al. (2012) CD200R1 Supports HSV-1 Viral Replication and Licenses Pro-Inflammatory Signaling Functions of TLR2. PLoS ONE 7(10): e47740. doi:10.1371/journal.pone.0047740. Link to article on publisher's website