Serotype 1 and 8 Pneumococci Evade Sensing by Inflammasomes in Human Lung Tissue
Serotype 1 and 8 Pneumococci Evade Sensing by Inflammasomes in Human Lung Tissue
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DOI：
10.1371/journal.pone.0137108
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发表时间：
2015-08-28
期刊：
影响因子：
3.7
通讯作者：
Opitz, Bastian
中科院分区：
文献类型：
--
作者：
Fatykhova, Diana;Rabes, Anne;Opitz, Bastian
肺炎链球菌是肺炎、败血症和脑膜炎的主要原因。肺炎球菌溶血素是肺炎链球菌的关键毒力因子。肺炎，其可以被NLRP 3炎性体感测。在超过90种血清型中，血清型1肺炎球菌（特别是MLST 306）已经在地球仪中作为侵袭性疾病的主要原因出现。然而，其特殊性的原因并不完全清楚。因此，我们研究了人类细胞中的肺炎球菌感染和模仿下呼吸道感染的人类肺器官培养系统。我们证明，不同的肺炎球菌血清型差异激活炎性小体依赖性IL-1 β在人类肺组织和细胞的生产。表达完全溶血性肺炎球菌溶血素的血清型2、3、6 B、9 N肺炎球菌激活NLRP 3炎性小体依赖性应答，而表达非溶血性毒素的血清型1和8菌株是IL-1 β产生的不良激活剂。因此，纯化的溶血性肺炎球菌溶血素而不是血清型1相关的非溶血性毒素激活人肺中的强IL-1 β产生。我们的数据表明，逃避炎性小体依赖的先天免疫反应的血清1型肺炎球菌可能有助于他们的能力，导致人类的侵袭性疾病。
Streptococcus pneumoniae is a major cause of pneumonia, sepsis and meningitis. The pore-forming toxin pneumolysin is a key virulence factor of S. pneumoniae, which can be sensed by the NLRP3 inflammasome. Among the over 90 serotypes, serotype 1 pneumococci (particularly MLST306) have emerged across the globe as a major cause of invasive disease. The cause for its particularity is, however, incompletely understood. We therefore examined pneumococcal infection in human cells and a human lung organ culture system mimicking infection of the lower respiratory tract. We demonstrate that different pneumococcal serotypes differentially activate inflammasome-dependent IL-1 beta production in human lung tissue and cells. Whereas serotype 2, 3, 6B, 9N pneumococci expressing fully haemolytic pneumolysins activate NLRP3 inflammasome-dependent responses, serotype 1 and 8 strains expressing non-haemolytic toxins are poor activators of IL-1 beta production. Accordingly, purified haemolytic pneumolysin but not serotype 1-associated non-haemolytic toxin activates strong IL-1 beta production in human lungs. Our data suggest that the evasion of inflammasome-dependent innate immune responses by serotype 1 pneumococci might contribute to their ability to cause invasive diseases in humans.