Importance of the pro-inflammatory effects of the capsule during invasive Streptococcus pneumoniae infection

侵袭性肺炎链球菌感染期间胶囊促炎作用的重要性

• 批准号: MR/K00168X/1
• 负责人: Jimstan Periselneris
• 金额: $ 29.15万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FK00168X%2F1
• 关键词: Importance; pro; inflammatory; effects; capsule

Streptococcus pneumoniae is the second most common cause of fatal bacterial infection world wide, causing half of all pneumonias and is also a frequent cause of meningitis and septicaemia. While the body's immune response results in the recruitment of white blood cells allowing the killing of the foreign organisms, the resulting inflammation can also cause damage to the body's own tissues. The pneumococcus is surrounded by a capsule made of sugars, which is important for the bacteria to evade being killed by white blood cells. However recent data from Drs Brown and Noursadeghi's laboratories has shown the capsule also affects the inflammatory response to pneumococcus, surprisingly resulting in increased pro-inflammatory responses. This effect could critically affect the development of invasive disease and inflammatory complications of severe infection such as septic shock. Furthermore, there are over 90 variations in pneumococcal capsule (serotypes), which are known to vary in severity and type of disease. These variations could be partially mediated by differences between serotypes in their effects on inflammation. By examining the affects of the capsule on the inflammatory response and the mechanisms underpinning it I hope to identify potential targets for therapeutic intervention and to improve our understanding of disease development, and thus reduce the morbidity and mortality of pneumococcus.

肺炎链球菌是世界范围内致命细菌感染的第二大常见原因，造成所有肺炎的一半，也是脑膜炎和败血症的常见原因。虽然身体的免疫反应导致白色血细胞的募集，从而允许杀死外来生物体，但由此产生的炎症也会对身体自身的组织造成损害。肺炎球菌被一层由糖组成的包膜所包围，这对于细菌避免被白色血细胞杀死很重要。然而，来自布朗博士和Noursadeghi实验室的最新数据表明，胶囊也会影响对肺炎球菌的炎症反应，令人惊讶地导致促炎反应增加。这种效应可能严重影响侵袭性疾病和严重感染的炎性并发症（如败血性休克）的发展。此外，肺炎球菌荚膜（血清型）有90多种变异，已知其在疾病的严重程度和类型上各不相同。这些变化可能部分由血清型之间对炎症作用的差异介导。通过研究胶囊对炎症反应的影响及其机制，我希望确定潜在的治疗干预目标，并提高我们对疾病发展的理解，从而降低肺炎球菌的发病率和死亡率。

项目成果

A Quorum-Sensing System That Regulates Streptococcus pneumoniae Biofilm Formation and Surface Polysaccharide Production.

• DOI: 10.1128/msphere.00324-17
• 发表时间: 2017-09
• 期刊: mSphere
• 影响因子: 4.8
• 作者: Junges R;Salvadori G;Shekhar S;Åmdal HA;Periselneris JN;Chen T;Brown JS;Petersen FC
• 通讯作者: Petersen FC

TLR-mediated inflammatory responses to Streptococcus pneumoniae are highly dependent on surface expression of bacterial lipoproteins.

• DOI: 10.4049/jimmunol.1401413
• 发表时间: 2014-10-01
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Tomlinson G;Chimalapati S;Pollard T;Lapp T;Cohen J;Camberlein E;Stafford S;Periselneris J;Aldridge C;Vollmer W;Picard C;Casanova JL;Noursadeghi M;Brown J
• 通讯作者: Brown J

Exposure to welding fumes and lower airway infection with Streptococcus pneumoniae.

• DOI: 10.1016/j.jaci.2015.06.033
• 发表时间: 2016-02
• 期刊: The Journal of allergy and clinical immunology
• 作者: Suri R;Periselneris J;Lanone S;Zeidler-Erdely PC;Melton G;Palmer KT;Andujar P;Antonini JM;Cohignac V;Erdely A;Jose RJ;Mudway I;Brown J;Grigg J
• 通讯作者: Grigg J