Soberman, RoyMacKay, Christopher R.Vaine, ChristineRyan, Glennice BowenCerny, Anna M.Thompson, Mikayla R.Nikolic, BorisPrimo, ValeriaChristmas, PeterSheiffele, PaulAronov, LisaKnipe, DavidKurt-Jones, Evelyn A.2013-04-082012Soberman, 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): e47740.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:10511334The 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.en-USBiologyImmunologyImmune ResponseMicrobiologyImmunityInflammationInnate ImmunityVirologyViral Transmission and InfectionHost CellsMedicineInfectious DiseasesViral DiseasesHerpes SimplexJournal Article2013-04-0810.1371/journal.pone.0047740