Toll-like receptors: key players in antiviral immunity

Abstract

TLRs are a family of innate receptors whose specificities are predetermined in the germline. Therefore, TLRs have evolved to recognize conserved features of microbes. Viruses typically lack the conserved features common to other pathogen classes, so the innate immune system has evolved to recognize viral nucleic acid as a hallmark of viral infection. In this review we discuss examples of TLR-mediated viral recognition and the functional consequences of this recognition for antiviral immunity.

Figure 1. Functional Consequences of TLR Signaling

Engulfed viruses are degraded in endosomes and/or phagosomes. Released viral nucleic acid stimulates intracellular nucleic acid-sensing TLRs (red) leading to phagosome autonomous responses including recruitment of V-ATPase (green) and NADPH oxidase (purple). Viral antigens generated upon degradation of the virus are loaded into MHC class II and shuttled to the surface (pink). In certain cell types, antigens are loaded into MHC class I via cross presentation (dashed line, green). TLR activation also leads to the upregulation of costimulatory molecules, CD40 (brown) and CD86 (lime), as well as a signaling cascade that leads to the transcription of cytokine genes.