TLR9-Dependent Recognition of MCMV by IPC and DC Generates Coordinated Cytokine Responses that Activate Antiviral NK Cell Function

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...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2004-07, Vol.21 (1), p.107-119
Main Authors: Krug, Anne, French, Anthony R, Barchet, Winfried, Fischer, Jens A.A, Dzionek, Andrzej, Pingel, Jeanette T, Orihuela, Michael M, Akira, Shizuo, Yokoyama, Wayne M, Colonna, Marco
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing
Animals
Antigens, Differentiation
Cell growth
Chemokines
Cytokines - metabolism
Cytomegalovirus
Dendritic Cells - physiology
Deoxyribonucleic acid
DNA
DNA-Binding Proteins - physiology
Immune system
Infections
Interferons - metabolism
Interleukin-12 - metabolism
Killer Cells, Natural - physiology
Lymphocytes
Mice
Murine cytomegalovirus
Muromegalovirus - physiology
Myeloid Differentiation Factor 88
Receptors, Cell Surface - physiology
Receptors, Immunologic
Rheumatic diseases
Rodents
Spleen
Toll-Like Receptor 9
Virus Replication
Viruses
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Summary: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.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2004.06.007