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Cutting Edge: Antibody-Mediated TLR7-Dependent Recognition of Viral RNA¹

Department of Medicine, University of Massachusetts, Worcester, MA 01605

TLR7 recognizes the genome of ssRNA viruses such as Coxsackievirus B. Because TLR7 is expressed in intracellular compartments, viral RNA must be internalized before its recognition by TLR7. In this study, we define plasmacytoid dendritic cells (pDC) as peripheral blood mononuclear immune cells that respond to Coxsackievirus. pDC activation by Coxsackievirus B requires the presence of specific antiviral Abs. We show that Fc receptors mediate the recognition of virus-Ab complexes and that TLR7 is required for human and murine pDC production of cytokines. These data define a pathway by which intracellular TLR7 senses viral RNA and indicate a role for TLRs in association with Abs in sustaining virus-specific responses.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This research support was provided by National Institutes of Health Grants R01-AI049309 and R21-AI064681 (to R.W.F.) and K08-AI053542 (to J.P.W.).

² Address correspondence and reprint requests to Dr. Jennifer Wang, Department of Medicine, University of Massachusetts, LRB 219, 364 Plantation, Worcester, MA 01605. E-mail address: jennifer.wang{at}umassmed.edu

³ Abbreviations used in this paper: pDC, plasmacytoid dendritic cell; BMDC, bone marrow-derived DC; CVB, Coxsackievirus B; IC, immune complex; IRS, immunoregulatory DNA sequence; MOI, multiplicity of infection; WT, wild type; IVIG, intravenous immune globulin.

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