CARD9 mediates T cell inflammatory response in Coxsackievirus B3-induced acute myocarditis

Cardiovasc Pathol. 2020 Nov-Dec:49:107261. doi: 10.1016/j.carpath.2020.107261. Epub 2020 Jul 8.

Abstract

Cardiac inflammation in Coxsackievirus B3 (CVB3)-induced myocarditis is a consequence of viral-related cardiac injury and immune response. Caspase-associated recruitment domain 9 (CARD9) is a critical adaptor protein involved in transduction of signals from various innate pattern recognition receptors. In this study, the role of CARD9 in acute viral myocarditis was evaluated. CARD9-/- and C57BL/6 mice were infected with CVB3. On day 7 postinfection, myocardial tissue and blood samples were collected and examined. After CARD9 knockout, mRNA and protein levels of transforming growth factor-β(TGF-β), interleukin-17A(IL-17A), and CARD domain of B-cell CLL/lymphoma 10(BCL-10) in the myocardium were markedly lower in CARD9-/- mice than in C57BL/6 mice with CVB3-induced viral myocarditis. This trend was similar for the pathological scores for inflammation and serum levels of cytokines interleukin-6(IL-6), interleukin-10(IL-10), interferon -γ(IFN-γ), TGF-β, and IL-17A. These results suggest that the CARD9-mediated secretion of pro-inflammatory cytokines plays an important role in the immune response to acute viral myocarditis.

Keywords: CARD9; Coxsackievirus B3; acute viral myocarditis; immune response; inflammation.

MeSH terms

  • Animals
  • CARD Signaling Adaptor Proteins / deficiency
  • CARD Signaling Adaptor Proteins / genetics
  • CARD Signaling Adaptor Proteins / metabolism*
  • Coxsackievirus Infections / genetics
  • Coxsackievirus Infections / immunology
  • Coxsackievirus Infections / metabolism*
  • Coxsackievirus Infections / virology
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal
  • Enterovirus B, Human / immunology*
  • Host-Pathogen Interactions
  • Inflammation Mediators / metabolism
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myocarditis / genetics
  • Myocarditis / immunology
  • Myocarditis / metabolism*
  • Myocarditis / virology
  • Myocardium / immunology
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Signal Transduction
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / virology

Substances

  • CARD Signaling Adaptor Proteins
  • CARD9 protein, human
  • Cytokines
  • Inflammation Mediators