Systemic autoimmunity induced by the TLR7/8 agonist Resiquimod causes myocarditis and dilated cardiomyopathy in a new mouse model of autoimmune heart disease

Dis Model Mech. 2017 Mar 1;10(3):259-270. doi: 10.1242/dmm.027409.

Abstract

Systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) show significant heart involvement and cardiovascular morbidity, which can be due to systemically increased levels of inflammation or direct autoreactivity targeting cardiac tissue. Despite high clinical relevance, cardiac damage secondary to systemic autoimmunity lacks inducible rodent models. Here, we characterise immune-mediated cardiac tissue damage in a new model of SLE induced by topical application of the Toll-like receptor 7/8 (TLR7/8) agonist Resiquimod. We observe a cardiac phenotype reminiscent of autoimmune-mediated dilated cardiomyopathy, and identify auto-antibodies as major contributors to cardiac tissue damage. Resiquimod-induced heart disease is a highly relevant mouse model for mechanistic and therapeutic studies aiming to protect the heart during autoimmunity.

Keywords: Autoimmunity; Dilated cardiomyopathy; Heart disease; Model; Myocarditis; Resiquimod; Toll-like receptor 7/8.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / drug effects
  • Adoptive Transfer
  • Animals
  • Autoantibodies / blood
  • Autoimmunity / drug effects*
  • Cardiomyopathy, Dilated / chemically induced*
  • Cardiomyopathy, Dilated / complications
  • Cardiomyopathy, Dilated / immunology
  • Cardiomyopathy, Dilated / physiopathology
  • Disease Models, Animal
  • Female
  • Genetic Variation
  • Heart Function Tests
  • Imidazoles / adverse effects*
  • Immunity, Cellular / drug effects
  • Inflammation / pathology
  • Lymph Nodes / drug effects
  • Lymph Nodes / pathology
  • Male
  • Mutation / genetics
  • Myocarditis / chemically induced*
  • Myocarditis / complications
  • Myocarditis / immunology
  • Myocarditis / physiopathology
  • Myocardium / pathology
  • Spleen / pathology
  • Toll-Like Receptor 7 / agonists*
  • Toll-Like Receptor 7 / metabolism
  • Toll-Like Receptor 8 / agonists*
  • Toll-Like Receptor 8 / metabolism

Substances

  • Autoantibodies
  • Imidazoles
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8
  • resiquimod