Cutting Edge: Priming of CD8 T Cell Immunity to Herpes Simplex Virus Type 1 Requires Cognate TLR3 Expression InVivo

Abstract

Despite its potential for involvement in viral immunity, little evidence links TLR3 to adaptive antiviral responses. Here we show that TLR3 is required for the generation of CD8 T cell immunity to HSV-1. The magnitude of the gB-specific CD8 T cell response after flank infection by HSV-1 was significantly reduced in mice lacking TIR domain-containing adaptor-inducing IFN-β or TLR3, but not MyD88. Impaired CTL induction was evident in chimeric mice lacking TLR3 in bone marrow (BM)-derived cells. Among the dendritic cell subsets, TLR3 was expressed by CD8α+ dendritic cells, known to be involved in priming HSV-1–specific CD8 T cells. Use of mixed BM chimeras revealed that TLR3 and the MHC class I-restriction element must be expressed by the same BM-derived cell for effective priming. These data imply that a cognate linkage between TLR3 and MHC class I is required for efficient CTL priming to HSV-1.

Protective T cell immunity in mice following protein-TLR7/8 agonist-conjugate immunization requires aggregation, type I IFN, and multiple DC subsets

“…Others have also examined a requirement for coupling of antigen delivery to and TLR signaling in DCs in the generation of CD8 + T cell immunity through cross-presentation. Coactivation of DCs presenting protein or viral antigens with TLR3 or TLR4 ligands improved cross-presentation in vitro and in vivo (14,(76)(77)(78). By contrast, CD8 + T cell responses can be generated in vivo in the absence of TLR3 after immunization with protein antigens and poly (I:C) (79,80).…”

TLR3 deficiency renders astrocytes permissive to herpes simplex virus infection and facilitates establishment of CNS infection in mice

“…TLR3 has been reported to have impact on both innate and adaptive immune responses during virus infections in the periphery and CNS (13,20,21,28,29). To look into the innate response to HSV-2 infection, we isolated medulla spinalis from mice infected with HSV-2 for 6 days and examined expression of IFNs, IFN-stimulated genes, and inflammatory genes.…”

An inhibitor of cyclin-dependent kinases suppresses TLR signaling and increases the susceptibility of cancer patients to herpes viridae

“…33 Finally, cross-priming of antiviral CD8 + T cell immunity to HSV-1 requires cognate TLR3 expression in vivo, possibly on the CD8α + CD103 + langerin + dermal DC subset capable of migrating from the infected site to the draining lymph node. 31,54 Consistently, Casanova et al reported that a dominant mutation in the tlr3 gene increases susceptibility of infants to HSV-1 induced encephalitis. 55 Moreover, DC-mediated NK cell triggering was shown to be important in the absence of CD4 + T helper cells to mount a protective anti-HSV response by CD8 + T cells.…”

“…1). Based on the key role of Toll-like receptors (TLR) in the control of infections 30 and that of TLR2, 3 and 9 in controlling Herpes viridae-related insults, [31][32][33][34] we investigated the capacity of peripheral blood mononuclear cells (PBMC) to respond to synthetic TLR ligands such as the TLR3 ligand poly (I:C), by releasing IFNγ, as shown in healthy volunteers ( Fig. 2A).…”