The protective effect of interfering TLR9-IRF5 signaling pathway on the development of CVB3-induced myocarditis

Clin Immunol. 2019 Oct:207:24-35. doi: 10.1016/j.clim.2019.07.002. Epub 2019 Jul 4.

Abstract

Since toll-like receptor 9 (TLR9) or interferon regulatory factor 5 (IRF5) was reported to be associated with the development of myocarditis, we wondered if the TLR9-IRF5 pathway could contribute to the development of coxsackievirus B3 (CVB3)-induced myocarditis. We detected signaling molecules of TLR9-IRF5 pathway in CVB3-infected patients and mice. The results showed that TLR9, IRF5 and its downstream molecules such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were significantly increased, and the increase was correlated with the severity of heart injury during CVB3 infection. In addition, we demonstrated that an AAAG ODN with IRF5 interfering activities significantly decreased the levels of the TLR9-IRF5 pathway molecules in hearts, spleens as well as white blood cells, and alleviated the myocarditis in CVB3-infected mice. The data suggest that interfering TLR9-IRF5 pathway could be an approach to treat CVB3-induced myocarditis.

Keywords: Coxsackievirus B3; Interferon regulatory factor 5; Myocarditis; Oligodeoxynucleotide; Toll-like receptor 9.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Child
  • Child, Preschool
  • Coxsackievirus Infections / metabolism*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Enterovirus
  • Female
  • Gene Expression Regulation
  • Humans
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / metabolism*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Myocarditis / metabolism*
  • Myocarditis / virology*
  • Myocardium / pathology
  • Oligodeoxyribonucleotides / metabolism
  • Signal Transduction
  • Toll-Like Receptor 9

Substances

  • Cytokines
  • Interferon Regulatory Factors
  • Irf5 protein, mouse
  • Oligodeoxyribonucleotides
  • Tlr9 protein, mouse
  • Toll-Like Receptor 9