Title | A CD103 Conventional Dendritic Cell Surveillance System Prevents Development of Overt Heart Failure during Subclinical Viral Myocarditis. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | 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, Epelman S |
Journal | Immunity |
Volume | 47 |
Issue | 5 |
Pagination | 974-989.e8 |
Date Published | 2017 11 21 |
ISSN | 1097-4180 |
Keywords | Animals, Antigens, CD, Cardiovirus Infections, CD11b Antigen, CD8-Positive T-Lymphocytes, Cell Movement, Dendritic Cells, Encephalomyocarditis virus, Female, Heart Failure, Hematopoiesis, Immunologic Memory, Integrin alpha Chains, Male, Mice, Mice, Inbred C57BL, Myocarditis, Receptors, CCR2 |
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. |
DOI | 10.1016/j.immuni.2017.10.011 |
Alternate Journal | Immunity |
PubMed ID | 29166591 |
Grant List | K08 HL112826 / HL / NHLBI NIH HHS / United States PJT364831 / / CIHR / Canada R01 AI085043 / AI / NIAID NIH HHS / United States FDN148386 / / CIHR / Canada K08 HL123519 / HL / NHLBI NIH HHS / United States R01 HL139714 / HL / NHLBI NIH HHS / United States |
Submitted by kej2006 on June 6, 2018 - 4:13pm