Acute Chlamydia pneumoniae reinfection accelerates the development of insulin resistance and diabetes in obese C57BL/6 mice.
Acute Chlamydia pneumoniae reinfection accelerates the development of insulin resistance and diabetes in obese C57BL/6 mice.
复制标题
急性肺炎衣原体再感染会加速肥胖 C57BL/6 小鼠胰岛素抵抗和糖尿病的发展。
DOI：
10.1086/599796
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Kaltenboeck,Bernhard
中科院分区：
文献类型：
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作者：
Wang,Chengming;Gao,Dongya;Kaltenboeck,Bernhard
背景流行病学和病理学证据将高度流行的病原体与慢性炎症性疾病联系在一起，如2型糖尿病。动物模型有助于从机制上理解炎症性疾病的感染性增强，胰岛素抵抗是炎症性疾病的核心病理生理缺陷。方法利用小鼠模型，我们研究了胰岛素抵抗的进展以及感染(肺炎衣原体感染与未感染的对照组小鼠)、遗传背景(C57BL/6与A/J小鼠)、饮食脂肪浓度(27%对5%)和时间(接种后2、5、9或15周)的影响。结果在肥胖的C57BL/6小鼠中，肺炎衣原体感染诱导的胰岛素抵抗显著增加，并在细菌清除后持续很长时间。Acutec可产生循环中的肿瘤坏死因子-α。肺炎定植加重了胰岛素抵抗，但不会在继发衣原体感染期间原位释放肿瘤坏死因子-α。阿奇霉素或抗肿瘤坏死因子-α抗体可预防感染加重的胰岛素抵抗，但显著增加衣原体向心脏的传播。阿奇霉素治疗的小鼠不能消除C。接种后3周，肺炎衣原体的载量(42个基因组/100 mg)显著低于对照组(219个基因组/100 mg)和抗肿瘤坏死因子-α抗体处理组(3090个基因组/100 mg)。肺炎感染通过循环介质以一种遗传和营养受限的方式促进胰岛素抵抗的发展。与当前人类糖尿病流行的相关性仍有待确定，但这一发现具有潜在的重要意义，因为人类C的高患病率。全球肺炎感染
BackgroundEpidemiological and pathological evidence links highly prevalent pathogens to chronic inflammatory diseases, such as type 2 diabetes. Animal models contribute critically to the mechanistic understanding of infectious enhancement of inflammatory diseases, which share insulin resistance as the central pathophysiological defectMethodsWith use of a mouse model, we examined insulin resistance progression and the influence of infection (Chlamydia pneumoniae–infected vs. uninfected control mice), genetic background (C57BL/6 vs. A/J mice), dietary fat concentration (27% vs. 5%), and time (2, 5, 9, or 15 weeks after inoculation)ResultsIn obese C57BL/6 mice,C. pneumoniaeinfection induced significantly increased insulin resistance that persisted long after bacterial clearance. Circulating tumor necrosis factor (TNF)–α produced in response to acuteC. pneumoniaelung colonization exacerbated insulin resistance but not TNF-α released in situ during secondary chlamydial infection. Azithromycin or anti–TNF-α antibody prevented infection-exacerbated insulin resistance but significantly enhanced chlamydial dissemination to the heart. Azithromycin-treated mice did not eliminateC. pneumoniaefrom lungs by 3 weeks after inoculation but had significantly lower loads (42 genomes per 100 mg) than did control mice (219 genomes per 100 mg) or anti–TNF-α antibody–treated mice (3090 genomes per 100 mg)ConclusionsMurineC. pneumoniaeinfection enhanced insulin resistance development in a genetically and nutritionally restricted manner via circulating mediators. The relevance for the current human diabetes epidemic remains to be determined, but this finding is potentially important because of the high prevalence of humanC. pneumoniaeinfection worldwide