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Cutting Edge: Overlapping Functions of TLR7 and TLR9 for Innate Defense against a Herpesvirus Infection¹

Nicolas Zucchini^*,,, Gilles Bessou^*,,, Stephanie Traub^*,,, Scott H. Robbins^*,,, Satoshi Uematsu, Shizuo Akira, Lena Alexopoulou^*,, and Marc Dalod^2,*,,

^* Centre d’Immunologie de Marseille-Luminy, Université de la Méditerranée, Case 906, Marseille, France; Institut National de la Santé et de la Recherche Médicale, Unité 631, Marseille, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6102, Marseille, France; and Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan

As initially demonstrated with murine cytomegalovirus (MCMV), plasmacytoid dendritic cells (pDCs) are the major source of IFN-/β in response to a variety of viruses in vivo. However, contradictory results have been obtained pertaining to the mechanisms promoting IFN-/β production by pDCs in response to MCMV. In this study we show that TLR7 and TLR9 exert redundant functions for IFN-/β, IL-12p40, and TNF- production by pDCs in vivo during MCMV infection. In contrast, we confirm that systemic production of IL-12p70 strictly depends on TLR9. The combined loss of TLR7 and TLR9 recapitulates critical features of the phenotype of MyD88-deficient mice, including a dramatic decrease in systemic IFN-/β levels, an increase in viral load, and increased susceptibility to MCMV-induced mortality. This is the first demonstration of the implication of TLR7 in the recognition of a DNA virus.

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¹ This work was supported by an Action thématique et incitative sur programme Grant from the Centre National de la Recherche Scientifique (CNRS) to M.D., an Action thématique et incitative sur programme Grant from the CNRS to L.A., and a grant from the Association pour la Recherche sur le Cancer to M.D. N.Z. was supported by the Ministère de l’Enseignement Supérieur, de la Recherche et des Techniques. S.H.R. was supported by the Fondation pour la Recherche Médicale. S.T. received a CNRS postdoctoral fellowship. Centre d’Immunologie de Marseille-Luminy is supported by institutional grants from Institut National de la Santé et de la Recherche Médicale, CNRS, and the Université de la Méditerranée.

² Address correspondence and reprint requests to Dr. Marc Dalod, Centre d’Immunologie de Marseille-Luminy, Parc Scientifique de Luminy, Case 906, F-13288 Marseille Cedex 09, France. E-mail address: dalod{at}ciml.univ-mrs.fr

³ Abbreviations used in this paper: pDC, plasmacytoid dendritic cell; EGFP, enhanced GFP; MCMV, murine cytomegalovirus; WT, wild type.