Department of Medicine, Division of Infectious Diseases and Immunology
Immunology and Infectious Disease | Virology
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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Copyright: © Soberman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
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
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; Aronov, Lisa; Knipe, David M.; and Kurt-Jones, Evelyn A., "CD200R1 supports HSV-1 viral replication and licenses pro-inflammatory signaling functions of TLR2" (2012). GSBS Student Publications. 1799.