MyD88-dependent immunity to a natural model of vaccinia virus infection does not involve toll-like receptor 2

Michael L. Davies, Janet J. Sei, Nicholas A. Siciliano, Ren Huan Xu, Felicia Roscoe, Luis J. Sigal, Laurence C. Eisenlohr, Christopher C. Norbury

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Although the pattern recognition receptor Toll-like receptor 2 (TLR2) is typically thought to recognize bacterial components, it has been described to alter the induction of both innate and adaptive immunity to a number of viruses, including vaccinia virus (VACV). However, many pathogens that reportedly encode TLR2 agonists may actually be artifactually contaminated during preparation, possibly with cellular debris or merely with molecules that sensitize cells to be activated by authentic TLR2 agonists. In both humans and mice, the most relevant natural route of infection with VACV is through intradermal infection of the skin. Therefore, we examined the requirement for TLR2 and its signaling adaptor MyD88 in protective immunity to VACV after intradermal infection. We find that although TLR2 may recognize virus preparations in vitro and have a minor role in preventing dissemination of VACV following systemic infection with large doses of virus, it is wholly disposable in both control of virus replication and induction of adaptive immunity following intradermal infection. In contrast, MyD88 is required for efficient induction of CD4 T cell and B cell responses and for local control of virus replication following intradermal infection. However, even MyD88 is not required to induce local inflammation, inflammatory cytokine production, or recruitment of cells that restrict virus from spreading systemically after peripheral infection. Thus, an effective antiviral response does require MyD88, but TLR2 is not required for control of a peripheral VACV infection. These findings emphasize the importance of studying relevant routes of infection when examining innate sensing mechanisms.

Original languageEnglish (US)
Pages (from-to)3557-3567
Number of pages11
JournalJournal of virology
Volume88
Issue number6
DOIs
StatePublished - Mar 2014

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Davies, M. L., Sei, J. J., Siciliano, N. A., Xu, R. H., Roscoe, F., Sigal, L. J., Eisenlohr, L. C., & Norbury, C. C. (2014). MyD88-dependent immunity to a natural model of vaccinia virus infection does not involve toll-like receptor 2. Journal of virology, 88(6), 3557-3567. https://doi.org/10.1128/JVI.02776-13