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Journal of Virology, May 2005, p. 5507-5515, Vol. 79, No. 9
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.9.5507-5515.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Inhibition of Toll-Like Receptor 7- and 9-Mediated Alpha/Beta Interferon Production in Human Plasmacytoid Dendritic Cells by Respiratory Syncytial Virus and Measles Virus

Jörg Schlender,1,{dagger} Veit Hornung,2,{dagger} Stefan Finke,1 Margit Günthner-Biller,2 Sabrina Marozin,1 Krzysztof Brzózka,1 Sharareh Moghim,1 Stefan Endres,2 Gunther Hartmann,2 and Karl-Klaus Conzelmann1*

Max von Pettenkofer Institute and Gene Center,1 Division of Clinical Pharmacology, Department of Internal Medicine, Ludwig-Maximilians-Universität München, Munich, Germany2

Received 2 November 2004/ Accepted 27 December 2004

Human plasmacytoid dendritic cells (PDC) are key sentinels alerting both innate and adaptive immune responses through production of huge amounts of alpha/beta interferon (IFN). IFN induction in PDC is triggered by outside-in signal transduction pathways through Toll-like receptor 7 (TLR7) and TLR9 as well as by recognition of cytosolic virus-specific patterns. TLR7 and TLR9 ligands include single-stranded RNA and CpG-rich DNA, respectively, as well as synthetic derivatives thereof which are being evaluated as therapeutic immune modulators promoting Th1 immune responses. Here, we identify the first viruses able to block IFN production by PDC. Both TLR-dependent and -independent IFN responses are abolished in human PDC infected with clinical isolates of respiratory syncytial virus (RSV), RSV strain A2, and measles virus Schwarz, in contrast to RSV strain Long, which we previously identified as a potent IFN inducer in human PDC (Hornung et al., J. Immunol. 173:5935-5943, 2004). Notably, IFN synthesis of PDC activated by the TLR7 and TLR9 agonists resiquimod (R848) and CpG oligodeoxynucleotide 2216 is switched off by subsequent infection by RSV A2 and measles virus. The capacity of RSV and measles virus of human PDC to shut down IFN production should contribute to the characteristic features of these viruses, such as Th2-biased immune pathology, immune suppression, and superinfection.

* Corresponding author. Mailing address: Max-von-Pettenkofer Institute and Gene Center, Feodor-Lynen-Str. 25, D-81377 Munich, Germany. Phone: 49 89 2180 76851. Fax: 49 89 2180 76899. E-mail: conzelma{at}lmb.uni-muenchen.de.

{dagger} J.S. and V.H. contributed equally to this work.

Journal of Virology, May 2005, p. 5507-5515, Vol. 79, No. 9
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.9.5507-5515.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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