Rotavirus infection accelerates type 1 diabetes in mice with established insulitis
Rotavirus infection accelerates type 1 diabetes in mice with established insulitis
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DOI：
10.1128/jvi.00597-08
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发表时间：
2008-07-01
影响因子：
5.4
通讯作者：
Coulson, Barbara S.
中科院分区：
文献类型：
--
作者：
Graham, Kate L.;Sanders, Natalie;Coulson, Barbara S.
感染调节I型糖尿病，这是一种常见的自身免疫性疾病，其特征在于胰腺中产生胰岛素的胰岛β细胞的破坏。儿童轮状病毒感染与胰岛自身免疫的恶化有关。非肥胖型糖尿病（NOD）小鼠发生淋巴细胞性胰岛浸润（胰岛炎），然后发生临床糖尿病，而NOD 8.3 TCR小鼠（对重要的胰岛自身抗原特异性的T细胞受体（TCR）转基因）显示出更快的糖尿病发作。用猴轮状病毒株RRV口服感染NOD幼鼠可延缓糖尿病的发展。在这里，一旦确定胰岛炎，RRV感染对糖尿病发展的影响被确定。NOD和NOD 8.3 TCR小鼠分别接种>= 12周龄和5周龄的RRV。在两种模型中，糖尿病发病均显著加速（P < 0.024），尽管RRV感染无症状且局限于肠道。糖尿病加重程度与血清抗RRV抗体滴度有关。RRV感染的NOD小鼠表现出增加胰岛炎发展的可能趋势。受感染的男性显示胰岛中CD8（+）T细胞比例增加。至少在一种模型中，β细胞主要组织相容性复合物I类表达和胰岛肿瘤坏死因子α mRNA水平升高。在自然实验中，NOD小鼠暴露于小鼠轮状病毒也会加速糖尿病。因此，β细胞自身免疫建立后的轮状病毒感染影响胰岛炎并使糖尿病恶化。一种可能的机制涉及β细胞对免疫识别的暴露增加和促炎细胞因子对自身反应性T细胞的激活。相对于小鼠年龄和胰岛炎程度的感染时间决定了糖尿病发作是否延迟、不变或加速。
Infection modulates type I diabetes, a common autoimmune disease characterized by the destruction of insulin-producing islet beta cells in the pancreas. Childhood rotavirus infections have been associated with exacerbations in islet autoimmunity. Nonobese diabetic (NOD) mice develop lymphocytic islet infiltration (insulitis) and then clinical diabetes, whereas NOD8.3 TCR mice, transgenic for a T-cell receptor (TCR) specific for an important islet autoantigen, show more rapid diabetes onset. Oral infection of infant NOD mice with the monkey rotavirus strain RRV delays diabetes development. Here, the effect of RRV infection on diabetes development once insulitis is established was determined. NOD and NOD8.3 TCR mice were inoculated with RRV aged >= 12 and 5 weeks, respectively. Diabetes onset was significantly accelerated in both models (P < 0.024), although RRV infection was asymptomatic and confined to the intestine. The degree of diabetes acceleration was related to the serum antibody titer to RRV. RRV-infected NOD mice showed a possible trend toward increased insulitis development. Infected males showed increased CD8(+) T-cell proportions in islets. Levels of beta-cell major histocompatibility complex class I expression and islet tumor necrosis factor alpha mRNA were elevated in at least one model. NOD mouse exposure to mouse rotavirus in a natural experiment also accelerated diabetes. Thus, rotavirus infection after beta-cell autoimmunity is established affects insulitis and exacerbates diabetes. A possible mechanism involves increased exposure of beta cells to immune recognition and activation of autoreactive T cells by proinflammatory cytokines. The timing of infection relative to mouse age and degree of insulitis determines whether diabetes onset is delayed, unaltered, or accelerated.