心肌炎
巨噬细胞极化
巨噬细胞
过继性细胞移植
免疫学
柯萨奇病毒
肿瘤坏死因子α
甘露糖受体
病毒性心肌炎
炎症
生物
细胞因子
脂多糖
医学
免疫系统
T细胞
内科学
病毒
肠道病毒
体外
生物化学
作者
Kang Li,Wei Xu,Qiang Guo,Zhenggang Jiang,Ping Wang,Ye Yan,Sidong Xiong
出处
期刊:Circulation Research
[Ovid Technologies (Wolters Kluwer)]
日期:2009-08-14
卷期号:105 (4): 353-364
被引量:186
标识
DOI:10.1161/circresaha.109.195230
摘要
Myocardial infiltrating macrophages play an important role in the pathogenesis of viral myocarditis in male BALB/c mice following coxsackievirus B3 (CVB3) infection. Interestingly, comparable macrophage numbers were observed in the myocardium of female mice during acute myocarditis.Given CVB3 infection causes severe myocarditis in male but not female mice, we postulated that macrophages infiltrating the myocardium of female mice may display distinct functional properties that contribute to differential susceptibility to CVB3 myocarditis.Here, we found that myocardial infiltrating macrophages from CVB3-infected male mice expressed high levels of classically activated macrophages (M1) markers, including inducible nitric oxide synthase, interleukin-12, tumor necrosis factor-alpha, and CD16/32, whereas those of females showed enhanced expression of arginase 1, interleukin-10, macrophage mannose receptor (MMR) and macrophage galactose type C-type lectin (MGL) that were associated with alternatively activated macrophage (M2) phenotype. Moreover, distinct myocardial-derived cytokines were found to play a critical role in differential macrophage polarization between sexes after CVB3 infection. Adoptive transfer of ex vivo programmed M1 macrophages, as expectedly, significantly increased myocarditis in both male and female mice. Strikingly, transfer of M2 macrophages into susceptible male mice remarkably alleviated myocardial inflammation by modulating local cytokine profile and promoting peripheral regulatory T cell (Treg) differentiation.Taken together, this study may facilitate the understanding of the mechanism underlying gender bias in susceptibility to CVB3 myocarditis and the development of therapeutic strategies based on macrophage polarization for inflammatory heart disease.
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