Innate Immunity, Lipid Signaling, and Chronic Infection

炎症是有效控制感染的关键；然而，在牙周病(PD)等慢性传染病中，由此产生的炎症无法充分保护宿主。与慢性广泛性帕金森病最相关的细菌是牙龈卟啉单胞菌。帕金森病的损害是通过牙周附着丧失、口腔骨丢失、单个核细胞大量涌入以及疾病部位炎性标志物的表达来识别的。这些促炎分子的表达部分是通过包括Toll样受体(TLR)在内的先天免疫模式识别受体来控制的。体外研究支持TLR信号通路在牙龈假单胞菌感染中调节炎症的作用；然而，这些 路径界定得很不明确。因此，有必要更详细地了解在牙龈假单胞菌的骨重建过程中调节炎症的宿主因素。 除了口腔局部炎性病变与牙龈假单胞菌感染有关外，最近的临床和动物模型数据支持牙龈假单胞菌和其他生物(包括肺炎衣原体)的感染在血管斑块加速积累中的作用。动脉粥样硬化是一种复杂的炎症性疾病。炎症的调节被认为是预防这种疾病的关键。 核激素受体肝X受体(LXR)在调节细胞胆固醇外流相关基因的表达中起着关键作用。最近，LXR的第二个功能，即调节TLR依赖的炎症通路已被发现。由于TLRs的先天免疫信号参与了动脉粥样硬化、PD和宿主对Pggivalis的反应，而LXR是TLR介导的炎症反应的调节因子，我们推测LXR可能同时影响Pggvalis诱发的口腔骨丢失和动脉粥样硬化。在这里，我们提出了一系列相互关联的目的，以检验LXR调节炎症基因表达和牙龈假单胞菌引起的骨丢失的假设；此外，LXR在感染加速的慢性炎性血管斑块积累中发挥核心作用。这些研究将提供对LXR在调节伴随牙龈假单胞菌感染的炎症中所起的作用的详细了解。

Inflammation is essential for effective control of infection; however, in chronic infectious diseases such as periodontal disease (PD), the resulting inflammation fails to adequately protect the host. The bacterium most associated with chronic generalized PD is Porphyromonas gingivalis. PD lesions are identified by loss of periodontal attachment, oral bone loss, significant influx of mononuclear cells, and expression of inflammatory markers at sites of disease. Expression of these pro-inflammatory molecules is controlled in part via innate immune pattern recognition receptors including the toll-like receptors (TLR). In vitro studies support roles for TLR signaling pathways regulate inflammation in response to P. gingivalis; however, these pathways are poorly defined. Therefore, a more detailed understanding of the host factors that regulate inflammation in response to P. gingivalis in the context of bone remodeling is needed. In addition to the local inflammatory lesions of the oral cavity associated with P. gingivalis infection, recent clinical and animal model data support a role for infection by organisms such as P. gingivalis and others including Chlamydophila pneumoniae with accelerated vascular plaque accumulation. Atherosclerosis is a complex inflammatory disease. Regulation of inflammation is thought to be key to preventing this disease. The nuclear hormone receptor liver X receptor (LXR) plays a key role in regulating expression of genes involved in cellular cholesterol efflux. Recently, a second function for LXR, namely regulation of TLRdependent inflammatory pathways has been identified. As innate immune signaling via TLRs is implicated in atherosclerosis, PD, and host response to P. gingivalis, and LXR is a regulator of TLR mediated inflammation, we speculated that LXR could influences both oral bone loss and atherosclerosis elicited by P. gingivalis. Here we propose an interrelated set of aims to test the hypothesis that LXR regulates inflammatory gene expression and bone loss elicited by P. gingivalis; moreover, LXR plays a central role in infection-accelerated chronic inflammatory vascular plaque accumulation. These studies will provide a detailed understanding of the role played by LXR in regulating inflammation that accompanies P. gingivalis infection.