A CD103 + Conventional Dendritic Cell Surveillance System Prevents Development of Overt Heart Failure during Subclinical Viral Myocarditis

Immunity. 2017 Nov 21;47(5):974-989.e8. doi: 10.1016/j.immuni.2017.10.011.

Abstract

Innate and adaptive immune cells modulate heart failure pathogenesis during viral myocarditis, yet their identities and functions remain poorly defined. We utilized a combination of genetic fate mapping, parabiotic, transcriptional, and functional analyses and demonstrated that the heart contained two major conventional dendritic cell (cDC) subsets, CD103+ and CD11b+, which differentially relied on local proliferation and precursor recruitment to maintain their tissue residency. Following viral infection of the myocardium, cDCs accumulated in the heart coincident with monocyte infiltration and loss of resident reparative embryonic-derived cardiac macrophages. cDC depletion abrogated antigen-specific CD8+ T cell proliferative expansion, transforming subclinical cardiac injury to overt heart failure. These effects were mediated by CD103+ cDCs, which are dependent on the transcription factor BATF3 for their development. Collectively, our findings identified resident cardiac cDC subsets, defined their origins, and revealed an essential role for CD103+ cDCs in antigen-specific T cell responses during subclinical viral myocarditis.

Keywords: T cells; dendritic cells; heart failure; myocarditis; ontogeny; virus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, CD / analysis*
  • CD11b Antigen / analysis
  • CD8-Positive T-Lymphocytes / immunology
  • Cardiovirus Infections / complications*
  • Cardiovirus Infections / immunology
  • Cell Movement
  • Dendritic Cells / immunology*
  • Encephalomyocarditis virus*
  • Female
  • Heart Failure / prevention & control*
  • Hematopoiesis
  • Immunologic Memory
  • Integrin alpha Chains / analysis*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myocarditis / complications*
  • Myocarditis / immunology
  • Receptors, CCR2 / physiology

Substances

  • Antigens, CD
  • CD11b Antigen
  • Ccr2 protein, mouse
  • Integrin alpha Chains
  • Receptors, CCR2
  • alpha E integrins