Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 9, Issue 11, Pages 1304-1312Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2009.07.014
Keywords
Viral myocarditis; Dendritic cells; Inflammation; Chemokines
Categories
Funding
- Natural Science Foundation of China [30772021]
- New Century of Ministry Education for Talented Man [06-0354]
- Ministry of Science and Technology China [2007CB572003]
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Myocarditis is associated with increased number of CD4(+) T cells in the myocardium after coxsackievirus B3 (CVB3) infection. Previous studies show that CD11c(+) myeloid dendritic cells (mDC) loaded with myosin could induce myocarditis. This study aims to investigate the generation and accumulation of mDC in CVB3-induced myocarditis. The presence of mDC in myocardium was detected by immunohistochemisty. Bone marrow-marrow-derived mDC were generated from uninfected and CVB3-infected mice. The percentage of CD11c(+) mDC on cultured cells and mean fluorescence index (MFI) of double positive cells (CD11c(+)CD40(+), CD11c(+)CD80(+)) were measured by flow cytometry. The expression of chemokine receptors (CCR5, CCR7) on mDC and chemokines (CCL4, CCL19) in the myocardium was detected. The migration of mDC in response to CCL4 or CCL19 was measured by chemotaxis assay. Mature mDC were elevated in the myocardium from CVB3-infected mice. The percentage of mDC generated from CVB3-infected group was increased. The MFI of CD11c(+)CD40(+) and CD11c(+)CD80(+) was increased in CVB3-infected group. The mDC showed a down-regulation of CCR5 and unaffected CCR7 mRAN levels associated with elevated CCL4 and CCL19 in the myocardium in CVB3-infected group. Numbers of migrating bone marrow-derived mDC from CVB3-infected mice were increased in vitro. We conclude that CVB3 infection induced the greater generation of mDC from bone marrow and accumulation of mature mDC in myocardial tissues. This migration was associated with increased levels of both CCL4 and CCL19 in the heart tissue. These suggest that blocking the migration of mDC may provide a novel therapy for myocarditis. (C) 2009 Elsevier B.V. All rights reserved.
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