Diet-induced obesity in mice causes changes in immune responses and bone loss manifested by bacterial challenge
Diet-induced obesity in mice causes changes in immune responses and bone loss manifested by bacterial challenge
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DOI：
10.1073/pnas.0710335105
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发表时间：
2007-12-18
影响因子：
11.1
通讯作者：
Leeman, Susan
中科院分区：
文献类型：
--
作者：
Amar, Salomon;Zhou, Qingde;Leeman, Susan
肥胖被认为与细菌感染的易感性增加有关。然而，很少有研究检查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（一种与牙周炎密切相关的感染）的先天免疫应答的影响。用牙龈卟啉单胞菌经口或全身感染饮食诱导肥胖（DIO）小鼠和瘦型对照C57 BL/6小鼠，检测感染后牙周病理学和全身免疫反应。口腔感染牙龈卟啉单胞菌后，DIO小鼠的牙槽骨丢失水平显著高于瘦对照组。口腔微生物采样显示，在感染期间和感染后，DIO小鼠与瘦小鼠相比，牙龈卟啉单胞菌水平更高。此外，与瘦小鼠相比，暴露于口腔感染或全身接种活牙龈卟啉单胞菌的DIO动物在所有时间点均出现炎症反应减弱，TNF-α、IL-6和血清淀粉样蛋白A（SAA）表达降低。最后，与瘦小鼠相比，从患有DIO并暴露于牙龈卟啉单胞菌的小鼠收获的腹腔巨噬细胞表现出促炎细胞因子水平降低，并且当暴露于牙龈卟啉单胞菌LPS治疗时，暴露后30分钟，NF-κ B向TNF-α和IL-10启动子的募集显著减少。这些数据表明，肥胖干扰免疫系统适当响应牙龈卟啉单胞菌感染的能力，并表明这种免疫失调参与了在DIO小鼠中观察到的细菌感染后牙槽骨损失增加。
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 A gingivalis, mice with DIO had a significantly higher level of alveolar bone loss than the lean controls. Oral microbial sampling disclosed higher levels of A 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 A 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 A gingivalis exhibited reduced levels of proinflammatory cytokines compared with lean mice and when exposed to A gingivalis LPS treatment had a significantly reduced recruitment of NF-kappa B 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.