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Cited by 405Viral Infections and Immunology ResearchImmunotherapy and Immune ResponsesCardiac Fibrosis and Remodeling

Dendritic cell–induced autoimmune heart failure requires cooperation between adaptive and innate immunity

Eriksson, Urs, Ricci, Romeo, Hunziker, Lukas, Kurrer, Michael O, Oudit, Gavin Y, Watts, Tania H, Sonderegger, Ivo, Bachmaier, Kurt +2 more·2003·Nature Medicine
DOI 10.1038/nm960
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Abstract

Genetic susceptibility and autoimmunity triggered by microbial infections are factors implicated in the pathogenesis of dilated cardiomyopathy, the most common cause of heart failure in young patients. Here we show that dendritic cells (DCs) loaded with a heart-specific self peptide induce CD4+ T-cell-mediated myocarditis in nontransgenic mice. Toll-like receptor (TLR) stimulation, in concert with CD40 triggering of self peptide-loaded dendritic cells, was shown to be required for disease induction. After resolution of acute myocarditis, DC-immunized mice developed heart failure, and TLR stimulation of these mice resulted in relapse of inflammatory infiltrates. Injection of damaged, syngeneic cardiomyocytes also induced myocarditis in mice if TLRs were activated in vivo. DC-induced myocarditis provides a unifying theory as to how tissue damage and activation of TLRs during infection can induce autoimmunity, relapses and cardiomyopathy.

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Crossref · 10.1038/nm960

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40 of 40 references verified0 citation errors · 0 not checkable

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  • Adoptive transfer of in vitro activated dendritic cells loaded with α-MyHC peptides can induce autoimmune myocarditis by activating heart-targeting T cells.

    “the adoptive transfer of in vitro activated dendritic cells loaded with α -MyHC peptides can induce autoimmune myocarditis by activating heart-targeting T cells”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [131]

  • Animal models demonstrate that myocarditis is an autoimmune disease that requires TLR activation by microbes.

    “Animal models of myocarditis have yielded a wealth of information about the pathogenesis of disease including a number of landmark articles that demonstrate that myocarditis is an autoimmune disease that requires TLR activation by microbes. 44,152,153”

    From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [152]

  • The majority of immune cells in the heart during acute myocarditis in EAM, autoimmune CVB3 myocarditis model, and humans are CD11b+ cells that include neutrophils, macrophages, mast cells, and some dendritic cells.

    “The majority of immune cells in the heart during acute myocarditis in EAM, the autoimmune CVB3 myocarditis model, and humans are CD11b+ cells that include neutrophils, macrophages, mast cells, and some dendritic cells. 124,146,152,159”

    From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [152]

  • The TLR4, caspase-1, and NLRP3 pathways are upregulated in patients, EAM, autoimmune CVB3 myocarditis, and CVB3-only models and increase IL-1β and IL-18 levels in the heart.

    “Another key pathway upregulated in patients, EAM, autoimmune CVB3 myocarditis, and CVB3only models is the TLR4, caspase-1, and NLRP3 pathways that increase IL-1 β and IL-18 levels in the heart. 124,146,152,156,161-164”

    From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [152]

  • Type I and II IFNs are a dominant immune response in CVB3 myocarditis models and EAM, where inhibition of these pathways leads to increased viral replication, pericardial and myocardial inflammation, and DCM.

    “Type I and II IFNs are a dominant immune response in CVB3 myocarditis models (and EAM) where inhibition of these pathways leads to increased viral replication, pericardial and myocardial inflammation, and DCM. 124,128,152,169,170”

    From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [152]

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Authors
Eriksson, U., Ricci, R., Hunziker, L., Kurrer, M. O., Oudit, G. Y., Watts, T. H., Sonderegger, I., Bachmaier, K., Kopf, M., & Penninger, J. M.
Affiliations
  • Institute of Molecular Biotechnology (AT)
  • University Hospital of Basel (CH)
  • University Hospital Zurich (CH)
  • University of Toronto (CA)
  • ETH Zurich (CH)
Corresponding author
  • Eriksson, Urs
  • Penninger, Josef M
ORCID
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2003-11-16
Volume
9
Issue
12
Pages
1484-1490
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/nm960
OpenAlex
W2040977790
Cited by
405
References
40
Citations by year
2026: 6 · 2025: 9 · 2024: 11 · 2023: 16 · 2022: 10 · 2021: 15 · 2020: 13 · 2019: 13 · 2018: 12 · 2017: 14 · 2016: 16 · 2015: 12 · 2014: 16 · 2013: 20 · 2012: 18
FWCI
21.33
Type
journal article
Language
en
Update notices
erratum (2004-01-01)
Open access
closed
Licence
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
Keywords
dendritic cells, dilated cardiomyopathy, heart failure, autoimmunity, myocarditis, Toll-like receptors, CD40, CD4+ T cells, self-peptides, innate immunity, adaptive immunity, infection-triggered autoimmunity, cardiomyocyte injury, recurrence
MeSH terms
Adaptation, Physiological, Animals, Autoantigens, Cardiomyopathy, Dilated, Dendritic Cells, Humans, Immunity, Innate, Membrane Glycoproteins, Mice, Inbred BALB C, Peptide Fragments, Receptors, Cell Surface, CD4-Positive T-Lymphocytes, Autoimmunity, Mice, SCID, Mice, Knockout, Models, Immunological, CD40 Antigens, Ventricular Myosins, Toll-Like Receptors, Mice

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