The Role of Toll-Like Receptors in the Induction of Immune Responses During Rabies Virus Infection

Jianwei Li, Milosz Faber, Bernhard Dietzschold, D. Craig Hooper

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

The host response to infection generally begins with interactions between pathogen-associated molecular patterns common to a variety of infectious agents and reciprocal pattern-recognition receptors (PRRs) expressed by cells of the innate immune system. The innate responses triggered by these interactions contribute to the early, innate control of infection as well as the induction of pathogen-specific adaptive immunity. The outcome of infection with wild-type rabies virus is particularly dependent upon the rapid induction of innate and adaptive immune mechanisms that can prevent the virus from reaching central nervous system (CNS) tissues, where it can evade immune clearance. However, laboratory strains that reach the CNS can be cleared, and this has evidently occurred in individuals with rabies. Therefore, PRRs may be active in the periphery and the CNS during rabies virus infection, possibly depending upon the nature of the infecting virus. To investigate these possibilities, we first examined the outcome of infection with attenuated rabies virus in mice lacking MyD88, an adaptor protein that is used to activate the transcription factor NF-κB by a number of PRRs including all of the Toll-like receptors (TLRs) except for TLR3. Finding that attenuated rabies virus mediates lethal disease in the absence of MyD88, we then examined the effects of the deletion of receptors using MyD88 including TLRs 2, 4, 7, and 9 as well as IL-1-receptor 1, and IFN-αβR on infection. Only mice lacking TLR7 exhibited a phenotype, with mortality intermediate between MyD88-/- and control mice with deficits in both the development of peripheral immunity and rabies virus clearance from the CNS.

Original languageEnglish
Pages (from-to)115-126
Number of pages12
JournalAdvances in Virus Research
Volume79
DOIs
StatePublished - 2011
Externally publishedYes

Keywords

  • Host response
  • Immunity
  • Rabies virus
  • Single-stranded RNA
  • TLR7

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