1. A CD103 + Conventional Dendritic Cell Surveillance System Prevents Development of Overt Heart Failure during Subclinical Viral Myocarditis.
- Author
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Clemente-Casares X, Hosseinzadeh S, Barbu I, Dick SA, Macklin JA, Wang Y, Momen A, Kantores C, Aronoff L, Farno M, Lucas TM, Avery J, Zarrin-Khat D, Elsaesser HJ, Razani B, Lavine KJ, Husain M, Brooks DG, Robbins CS, Cybulsky M, and Epelman S
- Subjects
- Animals, CD11b Antigen analysis, CD8-Positive T-Lymphocytes immunology, Cardiovirus Infections immunology, Cell Movement, Female, Hematopoiesis, Immunologic Memory, Male, Mice, Mice, Inbred C57BL, Myocarditis immunology, Receptors, CCR2 physiology, Antigens, CD analysis, Cardiovirus Infections complications, Dendritic Cells immunology, Encephalomyocarditis virus, Heart Failure prevention & control, Integrin alpha Chains analysis, Myocarditis complications
- 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., (Copyright © 2017 Elsevier Inc. All rights reserved.)- Published
- 2017
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