据英国《每日电讯报》报道，英国科学家宣布，他们发现了身体自然对抗引发肺炎和脑膜炎的肺炎链球菌的新方式，朝研制出治疗肺炎和脑膜炎的通用型疫苗又前进了一大步。该研究发表在《美国科学公共图书馆病原体》杂志上。
英国莱斯特大学和都柏林圣三一学院的研究人员在论文中以《理解上的巨大突破》为题，揭示了免疫系统如何对肺炎链球菌引发的感染作出反应的机制。
研究人员称，他们首次发现，肺炎会触发一群名叫炎性体的免疫系统蛋白。当被激发时，炎性体会启动一系列事件，导致包括白介素在内的活性分子的生成以对抗感染。科学家可以据此研发出新药物，这些药物能触发同样的反应，将疾病扼杀在萌芽状态。
莱斯特大学的阿拉斯卡迪格鲁和圣三一学院的艾德拉弗勒认为，这一关于毒素如何同免疫系统结合的新认知意味着研究人员可以研发出新疫苗。现在，对抗肺炎链球菌的疫苗可以防御7种不同的菌株，但新方法研发出的疫苗应该能够对抗所有92种菌株。
卡迪格鲁表示，这是一项非常令人兴奋的发现，提供了一种全新的方法来对抗细菌。这个“重大突破”将帮助科学家更好地理解每年造成数百万婴儿死亡以及很多老年人患病和死亡的肺炎和脑膜炎这两个罪魁祸首。
生物谷推荐英文摘要：
PLoS Pathog doi:10.1371/journal.ppat.1001191
Pneumolysin Activates the NLRP3 Inflammasome and Promotes Proinflammatory Cytokines Independently of TLR4
Edel A. McNeela1, áine Burke1, Daniel R. Neill2, Cathy Baxter1, Vitor E. Fernandes2, Daniela Ferreira2, Sarah Smeaton2, Rana El-Rachkidy2, Rachel M. McLoughlin3, Andres Mori1, Barry Moran3, Katherine A. Fitzgerald4, Jurg Tschopp5, Virginie Pétrilli5, Peter W. Andrew2, Aras Kadioglu2*, Ed C. Lavelle1*
1 Adjuvant Research Group, School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland, 2 Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom, 3 School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland, 4 Department of Medicine, University of Massachusetts, Worcester, Massachusetts, United States of America, 5 Department of Biochemistry, University of Lausanne, Epalinges, Switzerland
Pneumolysin (PLY) is a key Streptococcus pneumoniae virulence factor and potential candidate for inclusion in pneumococcal subunit vaccines. Dendritic cells (DC) play a key role in the initiation and instruction of adaptive immunity, but the effects of PLY on DC have not been widely investigated. Endotoxin-free PLY enhanced costimulatory molecule expression on DC but did not induce cytokine secretion. These effects have functional significance as adoptive transfer of DC exposed to PLY and antigen resulted in stronger antigen-specific T cell proliferation than transfer of DC exposed to antigen alone. PLY synergized with TLR agonists to enhance secretion of the proinflammatory cytokines IL-12, IL-23, IL-6, IL-1β, IL-1α and TNF-α by DC and enhanced cytokines including IL-17A and IFN-γ by splenocytes. PLY-induced DC maturation and cytokine secretion by DC and splenocytes was TLR4-independent. Both IL-17A and IFN-γ are required for protective immunity to pneumococcal infection and intranasal infection of mice with PLY-deficient pneumococci induced significantly less IFN-γ and IL-17A in the lungs compared to infection with wild-type bacteria. IL-1β plays a key role in promoting IL-17A and was previously shown to mediate protection against pneumococcal infection. The enhancement of IL-1β secretion by whole live S. pneumoniae and by PLY in DC required NLRP3, identifying PLY as a novel NLRP3 inflammasome activator. Furthermore, NLRP3 was required for protective immunity against respiratory infection with S. pneumoniae. These results add significantly to our understanding of the interactions between PLY and the immune system.
