Tobacco upregulates P. gingivalis fimbrial proteins which induce TLR2 hyposensitivity.
Tobacco upregulates P. gingivalis fimbrial proteins which induce TLR2 hyposensitivity.
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DOI：
10.1371/journal.pone.0009323
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发表时间：
2010-05-04
期刊：
影响因子：
3.7
通讯作者：
Scott DA
中科院分区：
文献类型：
--
作者：
Bagaitkar J;Demuth DR;Daep CA;Renaud DE;Pierce DL;Scott DA
吸烟者比不吸烟者更容易患牙周炎，但临床炎症迹象减少。根本机制尚不清楚。我们之前已经表明，香烟烟雾提取物（CSE）代表了牙龈卟啉单胞菌通过改变几种毒力因子（包括主要和次要菌毛抗原（分别为 FimA 和 Mfa1）和荚膜）的表达来适应环境应激，同时降低了完整牙龈卟啉单胞菌的促炎潜力。我们假设，CSE 对荚膜和菌毛基因的调节反映在超微结构和功能水平上，改变了宿主-病原体相互作用的性质，并有助于降低暴露于烟雾的牙龈卟啉单胞菌的促炎潜力。通过电子显微镜测定 CSE 诱导的超微结构改变，并通过蛋白质印迹和开放流动生物膜研究的生理后果证实。通过量化原代人类先天细胞和 OBA-9 细胞中的细胞因子诱导，确定特定 CSE 失调蛋白 rFimA 和 rMfa1 的炎症谱。 CSE 在蛋白质水平上调牙龈卟啉单胞菌 FimA，在超微结构水平上抑制荚膜多糖的产生，并创造促进生物膜形成的条件。我们进一步表明，虽然 FimA 被 TLR2/6 识别，但它在几种细胞类型中仅具有最小的炎症活性。此外，FimA 刺激以 IκBα 和 IRAK-1 依赖性方式长期消除其他 TLR-2 特异性激动剂（Pam3CSK4、FSL、Mfa1）随后 TLR2 刺激的促炎反应。这些研究提供了一些初步信息，从机制上解释烟草烟雾如何改变牙龈卟啉单胞菌表型，从而可能促进牙龈卟啉单胞菌定植和感染，同时减少宿主对这种主要粘膜病原体的反应。
Tobacco smokers are more susceptible to periodontitis than non-smokers but exhibit reduced signs of clinical inflammation. The underlying mechanisms are unknown. We have previously shown that cigarette smoke extract (CSE) represents an environmental stress to which P. gingivalis adapts by altering the expression of several virulence factors – including major and minor fimbrial antigens (FimA and Mfa1, respectively) and capsule – concomitant with a reduced pro-inflammatory potential of intact P. gingivalis. We hypothesized that CSE-regulation of capsule and fimbrial genes is reflected at the ultrastructural and functional levels, alters the nature of host-pathogen interactions, and contributes to the reduced pro- inflammatory potential of smoke exposed P. gingivalis. CSE induced ultrastructural alterations were determined by electron microscopy, confirmed by Western blot and physiological consequences studied in open-flow biofilms. Inflammatory profiling of specific CSE-dysregulated proteins, rFimA and rMfa1, was determined by quantifying cytokine induction in primary human innate and OBA-9 cells. CSE up-regulates P. gingivalis FimA at the protein level, suppresses the production of capsular polysaccharides at the ultrastructural level, and creates conditions that promote biofilm formation. We further show that while FimA is recognized by TLR2/6, it has only minimal inflammatory activity in several cell types. Furthermore, FimA stimulation chronically abrogates the pro-inflammatory response to subsequent TLR2 stimulation by other TLR-2-specific agonists (Pam3CSK4, FSL, Mfa1) in an IκBα- and IRAK-1-dependent manner. These studies provide some of the first information to explain, mechanistically, how tobacco smoke changes the P. gingivalis phenotype in a manner likely to promote P. gingivalis colonization and infection while simultaneously reducing the host response to this major mucosal pathogen.
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影响因子：
3.1
作者：
Billips, Benjamin K.;Schaeffer, Anthony J.;Klumpp, David J.
通讯作者：
Klumpp, David J.
影响因子：
3.4
作者：
Hajishengallis, George;Tapping, Richard I.;Yoshimura, Fuminobu
通讯作者：
Yoshimura, Fuminobu
影响因子：
7.6
作者：
Fraser, HS;Palmer, RM;Scott, DA
通讯作者：
Scott, DA
影响因子：
3.1
作者：
d'Empaire, Gabriela;Baer, Michael T.;Gibson, Frank C., III
通讯作者：
Gibson, Frank C., III
DOI：
10.1164/rccm.200311-1521oc
发表时间：
2004-12-01
影响因子：
24.7
作者：
Drannik, AG;Pouladi, MA;Stämpfli, MR
通讯作者：
Stämpfli, MR