TY - JOUR
T1 - Plasmacytoid Dendritic Cell Ablation Impacts Early Interferon Responses and Antiviral NK and CD8+ T Cell Accrual
AU - Swiecki, Melissa
AU - Gilfillan, Susan
AU - Vermi, William
AU - Wang, Yaming
AU - Colonna, Marco
N1 - Funding Information:
We would like to thank W. Yokoyama, T. Cheng, A. French, R. Presti (Washington University, St. Louis, MO), L. Lefrançois (University of Connecticut, Farmington, CT), and M. Brown (University of Virginia, Charlottesville, VA) for reagents and advice on virus infections; S. Jung for the DTR plasmid (Weizmann Institute of Science, Rehovot, Israel); S. McCartney and K. Otero (Washington University) for helping with injections; S. Schloemann and O. Malkova for cell sorting; M. White for injection of the BDCA2-DTR transgene and the SiglecH-eGFP ES cells; and M. Cella, M. Diamond, A. French, T. Hannan, and P. Allen for helpful discussions and critically reading the manuscript. M.S. is supported by the NRSA training grant 5T32DK007296-30. Y.W. is supported by the Pulmonary and Critical Care training grant 2T32HL007317-31 from the National Heart, Lung, and Blood Institute. This project was supported by Juvenile Diabetes Research Foundation grant 24-2007-420 and National Institutes of Health grant CA109673 to M.C.
PY - 2010/12/14
Y1 - 2010/12/14
N2 - Plasmacytoid dendritic cells (pDCs) mediate type I interferon (IFN-I) responses to viruses that are recognized through the Toll-like receptor 7 (TLR7) or TLR9 signaling pathway. However, it is unclear how pDCs regulate the antiviral responses via innate and adaptive immune cells. We generated diphtheria toxin receptor transgenic mice to selectively deplete pDCs by administration of diphtheria toxin. pDC-depleted mice were challenged with viruses known to activate pDCs. In murine cytomegalovirus (MCMV) infection, pDC depletion reduced early IFN-I production and augmented viral burden facilitating the expansion of natural killer (NK) cells expressing the MCMV-specific receptor Ly49H. During vesicular stomatitis virus (VSV) infection, pDC depletion enhanced early viral replication and impaired the survival and accumulation of virus-specific cytotoxic T lymphocytes. We conclude that pDCs mediate early antiviral IFN-I responses and influence the accrual of virus-specific NK or CD8+ T cells in a virus-dependent manner.
AB - Plasmacytoid dendritic cells (pDCs) mediate type I interferon (IFN-I) responses to viruses that are recognized through the Toll-like receptor 7 (TLR7) or TLR9 signaling pathway. However, it is unclear how pDCs regulate the antiviral responses via innate and adaptive immune cells. We generated diphtheria toxin receptor transgenic mice to selectively deplete pDCs by administration of diphtheria toxin. pDC-depleted mice were challenged with viruses known to activate pDCs. In murine cytomegalovirus (MCMV) infection, pDC depletion reduced early IFN-I production and augmented viral burden facilitating the expansion of natural killer (NK) cells expressing the MCMV-specific receptor Ly49H. During vesicular stomatitis virus (VSV) infection, pDC depletion enhanced early viral replication and impaired the survival and accumulation of virus-specific cytotoxic T lymphocytes. We conclude that pDCs mediate early antiviral IFN-I responses and influence the accrual of virus-specific NK or CD8+ T cells in a virus-dependent manner.
UR - http://www.scopus.com/inward/record.url?scp=78650178928&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2010.11.020
DO - 10.1016/j.immuni.2010.11.020
M3 - Article
C2 - 21130004
AN - SCOPUS:78650178928
SN - 1074-7613
VL - 33
SP - 955
EP - 966
JO - Immunity
JF - Immunity
IS - 6
ER -