Increased susceptibility of male BALB/c mice to coxsackievirus B3-induced myocarditis: role for CD1d
Increased susceptibility of male BALB/c mice to coxsackievirus B3-induced myocarditis: role for CD1d
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DOI：
10.1007/s00430-004-0221-6
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发表时间：
2005-05-01
影响因子：
5.4
通讯作者：
Huber, SA
中科院分区：
文献类型：
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作者：
Huber, SA
感染柯萨奇病毒B3(CVB3)H3变种的BALB/c雄性小鼠发生暴发性心肌炎。年龄匹配的雌性小鼠由于心肌细胞上病毒受体表达减少而表现出较少的心肌炎。感染后3天，男性血清中的肿瘤坏死因子α和白介素1β水平升高。在整个7天的观察期内，干扰素-γ水平上升较慢。CD4(+)、CD8(+)、巨噬细胞(Mac3+)和Gamma Delta(+)细胞均在男性心脏内聚集，其中Gamma Delta(+)细胞早期(第3天)浸润。雌性也积累了CD4(+)细胞，但其他类型的细胞很少。男性心脏中的CD4(+)细胞主要产生干扰素-γ，表明是Th1细胞表型，而女性的CD4(+)细胞主要产生IL-4，但很少产生干扰素-γ，表明是Th2表型。CD1d是一种主要的组织相容性复合体I类分子，在体内和体外，CVB3感染的雄性心肌细胞中CD1d表达增加，而雌性心肌细胞中CD1d表达增加。这些结果表明，CVB3感染在先天免疫和获得性免疫方面都会产生性别差异，这可能解释了疾病易感性的差异。
BALB/c male mice infected with the H3 variant of coxsackievirus B3 (CVB3) develop fulminant myocarditis. Age-matched female mice show little myocarditis due to decreased virus receptor expression on cardiac cells. TNF alpha and IL-1 beta levels were increased in males by 3 days after infection. IFN gamma levels increased more slowly throughout the 7-day observation period. CD4(+), CD8(+), macrophage (Mac3(+)) and gamma delta(+) cells all accumulated in male hearts, with gamma delta(+) cells showing early (day 3) infiltration. Females also accumulated CD4(+) cells, but few of the other cell types. CD4(+) cells in male hearts predominately produced IFN gamma, indicating a Th1 cell phenotype, whereas CD4(+) cells in females produced IL-4, but little IFN gamma, indicating a Th2 phenotype. CD1d, a major histocompatibility complex I-like molecule often implicated in innate immunity, was increased in CVB3-infected male but not female cardiocytes both in vivo and in vitro. These results demonstrate that CVB3 infections produce gender-specific differences in both innate and adaptive immunity, which may explain the difference in disease susceptibility.