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

Publication date: 21 November 2017
Source:Immunity, Volume 47, Issue 5
Author(s): Xavier Clemente-Casares, Siyavash Hosseinzadeh, Iulia Barbu, Sarah A. Dick, Jillian A. Macklin, Yiming Wang, Abdul Momen, Crystal Kantores, Laura Aronoff, Maylis Farno, Tiffany M. Lucas, Joan Avery, Dorrin Zarrin-Khat, Heidi J. Elsaesser, Babak Razani, Kory J. Lavine, Mansoor Husain, David G. Brooks, Clinton S. Robbins, Myron Cybulsky, Slava Epelman
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.

Teaser

Dendritic cells (DCs) within the myocardium are poorly characterized. Clemente-Casares et al. demonstrate that the myocardium contains heterogeneous conventional DC subsets that differentially utilize recruitment and proliferation to maintain residency. They identify a BATF3-dependent CD103⁺ cDC surveillance system that prevents the transition of subclinical viral myocarditis to overt heart failure.


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