Amar Salomon, Zhou Qingde, Shaik-Dasthagirisaheb Yazdani, Leeman Susan
Department of Periodontology and Oral Biology, School of Dental Medicine, School of Medicine, Boston University, Boston, MA 02118, USA.
Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20466-71. doi: 10.1073/pnas.0710335105. Epub 2007 Dec 12.
Obesity has been suggested to be associated with an increased susceptibility to bacterial infection. However, few studies have examined the effect of obesity on the immune response to bacterial infections. In the present study, we investigated the effect of obesity on innate immune responses to Porphyromonas gingivalis infection, an infection strongly associated with periodontitis. Mice with diet-induced obesity (DIO) and lean control C57BL/6 mice were infected orally or systemically with P. gingivalis, and periodontal pathology and systemic immune responses were examined postinfection. After oral infection with P. gingivalis, mice with DIO had a significantly higher level of alveolar bone loss than the lean controls. Oral microbial sampling disclosed higher levels of P. gingivalis in mice with DIO vs. lean mice during and after infection. Furthermore, animals with DIO exposed to oral infection or systemic inoculation of live P. gingivalis developed a blunted inflammatory response with reduced expression of TNF-alpha, IL-6, and serum amyloid A (SAA) at all time points compared with lean mice. Finally, peritoneal macrophages harvested from mice with DIO and exposed to P. gingivalis exhibited reduced levels of proinflammatory cytokines compared with lean mice and when exposed to P. gingivalis LPS treatment had a significantly reduced recruitment of NF-kappaB to both TNF-alpha and IL-10 promoters 30 min after exposure. These data indicate that obesity interferes with the ability of the immune system to appropriately respond to P. gingivalis infection and suggest that this immune dysregulation participates in the increased alveolar bone loss after bacterial infection observed in mice with DIO.
肥胖被认为与细菌感染易感性增加有关。然而，很少有研究探讨肥胖对细菌感染免疫反应的影响。在本研究中，我们调查了肥胖对牙龈卟啉单胞菌感染固有免疫反应的影响，牙龈卟啉单胞菌感染与牙周炎密切相关。对饮食诱导肥胖（DIO）小鼠和瘦对照C57BL/6小鼠进行口腔或全身牙龈卟啉单胞菌感染，并在感染后检查牙周病理学和全身免疫反应。牙龈卟啉单胞菌口腔感染后，DIO小鼠的牙槽骨吸收水平显著高于瘦对照小鼠。口腔微生物采样显示，感染期间及感染后，DIO小鼠的牙龈卟啉单胞菌水平高于瘦小鼠。此外，与瘦小鼠相比，经口腔感染或全身接种活牙龈卟啉单胞菌的DIO动物在所有时间点的炎症反应均减弱，肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和血清淀粉样蛋白A（SAA）的表达降低。最后，与瘦小鼠相比，从DIO小鼠获取并暴露于牙龈卟啉单胞菌的腹腔巨噬细胞促炎细胞因子水平降低，并且在暴露于牙龈卟啉单胞菌脂多糖（LPS）处理30分钟后，NF-κB向TNF-α和IL-10启动子的募集显著减少。这些数据表明，肥胖会干扰免疫系统对牙龈卟啉单胞菌感染的适当反应能力，并表明这种免疫失调参与了DIO小鼠细菌感染后观察到的牙槽骨吸收增加。
