TY - JOUR
T1 - TLR9-dependent recognition of MCMV by IPC and DC generates coordinated cytokine responses that activate antiviral NK cell function
AU - Krug, Anne
AU - French, Anthony R.
AU - Barchet, Winfried
AU - Fischer, Jens A.A.
AU - Dzionek, Andrzej
AU - Pingel, Jeanette T.
AU - Orihuela, Michael M.
AU - Akira, Shizuo
AU - Yokoyama, Wayne M.
AU - Colonna, Marco
N1 - Funding Information:
We would like to thank Carey A. Strader for performing TLR9 RT-PCR; Arthur M. Krieg (Coley Pharmaceutical Group, Wellesley, MA) and Hermann Wagner (Technical University of Munich, Germany) for providing TLR9 −/− mice; Kathy Frederick and Emil R. Unanue (Washington University, St. Louis, MO) for MyD88 −/− mice; William Eades (Siteman Cancer Center flow cytometry facility) for expert cell sorting; and Marina Cella and Susan Gilfillan (Washington University, St. Louis, MO) for advice and helpful discussions. A.K. was supported by the Deutsche Forschungsgemeinschaft (KR 2199/1-1). W.M.Y. is supported by NIH grants and is an investigator of the Howard Hughes Institute. The genotyping was supported by the Rheumatic Disease Core Center at Washington University School of Medicine.
PY - 2004/7
Y1 - 2004/7
N2 - Natural interferon-producing cells (IPC) respond to viruses by secreting type I interferon (IFN) and interleukin-12 (IL-12). Toll-like receptor (TLR) 9 mediates IPC recognition of some of these viruses in vitro. However, whether TLR9-induced activation of IPC is necessary for an effective antiviral response in vivo is not clear. Here, we demonstrate that IPC and dendritic cells (DC) recognize murine cytomegalovirus (MCMV) through TLR9. TLR9-mediated cytokine secretion promotes viral clearance by NK cells that express the MCMV-specific receptor Ly49H. Although depletion of IPC leads to a drastic reduction of the IFN-α response, this allows other cell types to secrete IL-12, ensuring normal IFN-γ and NK cell responses to MCMV. We conclude that the TLR9/MyD88 pathway mediates antiviral cytokine responses by IPC, DC, and possibly other cell types, which are coordinated to promote effective NK cell function and MCMV clearance.
AB - Natural interferon-producing cells (IPC) respond to viruses by secreting type I interferon (IFN) and interleukin-12 (IL-12). Toll-like receptor (TLR) 9 mediates IPC recognition of some of these viruses in vitro. However, whether TLR9-induced activation of IPC is necessary for an effective antiviral response in vivo is not clear. Here, we demonstrate that IPC and dendritic cells (DC) recognize murine cytomegalovirus (MCMV) through TLR9. TLR9-mediated cytokine secretion promotes viral clearance by NK cells that express the MCMV-specific receptor Ly49H. Although depletion of IPC leads to a drastic reduction of the IFN-α response, this allows other cell types to secrete IL-12, ensuring normal IFN-γ and NK cell responses to MCMV. We conclude that the TLR9/MyD88 pathway mediates antiviral cytokine responses by IPC, DC, and possibly other cell types, which are coordinated to promote effective NK cell function and MCMV clearance.
UR - http://www.scopus.com/inward/record.url?scp=3142683548&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2004.06.007
DO - 10.1016/j.immuni.2004.06.007
M3 - Article
C2 - 15345224
AN - SCOPUS:3142683548
SN - 1074-7613
VL - 21
SP - 107
EP - 119
JO - Immunity
JF - Immunity
IS - 1
ER -