mBio：揭示肺炎支原体引发呼吸道疾病的新机制

  近日，发表在国际杂志mBio上的一项研究报告中，来自德克萨斯大学健康科学中心的研究人员通过对哮喘及其它急慢性肺部疾病进行研究，揭示了细菌毒素引发严重机体炎症的一种新型机制，相关研究结果或有助开发潜在疗法从而为改善患者机体健康提供帮助。

  早在2006年研究人员就发现了一种肺炎支原体社区获得性呼吸窘迫综合症（CARDS）毒素，CARDS毒素被认为是继白喉毒素和百日咳毒素后又一个新型的关键细菌呼吸毒素。肺炎支原体是一种在肺部和呼吸道持续性感染的常见病原体，其可以产生对机体有害的CARDS毒素，该毒素可以和NALP3分子进行反应，而NALP3分子可以调节炎性通路，引发促炎性反应的过度激活。

  研究者Joel B. Baseman表示，炎症是一种机体应对感染和损伤的重要自我保护机制。但是当一种微生物因子，比如CARDS毒素控制炎性反应时，就会损伤机体；而CARDS毒素正可以通过这种新型机制来诱发加剧并延长炎性反应，进而导致组织损伤、呼吸道狭窄、粘液分泌过量以及咳嗽等后果。

  由于肺炎支原体感染在儿童及成年人中发生较为频繁，而CARDS毒素就是诱发炎症的一种强大的诱导物，因此经常会发生肺炎支原体及其它病原体之间的共感染，从而加重病情。如今研究人员鉴别出了细菌毒素引发疾病的新机制，将有助于后期开发新型疗法以抑制CARDS毒素的致病过程。（转化医学网360zhyx.com）
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转化医学网推荐的原文阅读：

ADP-Ribosylation of NLRP3 by Mycoplasma pneumoniae CARDS Toxin Regulates Inflammasome Activity
mBio doi: 10.1128/mBio.02186-14
Santanu Bosea, Jesus A. Segoviab, Sudha R. Somarajanb, Te-Hung Changb, T. R. Kannanb, Joel B. Basemanb
The inflammasome is a major regulator of inflammation through its activation of procaspase-1, which cleaves prointerleukin-1β (pro-IL-1β) into its mature form. IL-1β is a critical proinflammatory cytokine that dictates the severity of inflammation associated with a wide spectrum of inflammatory diseases. NLRP3 is a key component of the inflammasome complex, and multiple signals and stimuli trigger formation of the NLRP3 inflammasome complex. In the current study, we uncovered a yet unknown mechanism of NLRP3 inflammasome activation by a pathogen-derived factor. We show that the unique bacterial ADP-ribosylating and vacuolating toxin produced by Mycoplasma pneumoniae and designated community-acquired respiratory distress syndrome (CARDS) toxin activates the NLRP3 inflammasome by colocalizing with the NLRP3 inflammasome and catalyzing the ADP-ribosylation of NLRP3. Mutant full-length CARDS toxin lacking ADP-ribosyltransferase (ADPRT) activity and truncated CARDS toxins unable to bind to macrophages and be internalized failed to activate the NLRP3 inflammasome. These studies demonstrate that CARDS toxin-mediated ADP-ribosylation constitutes an important posttranslational modification of NLRP3, that ADPRT activity of CARDS toxin is essential for NLRP3 inflammasome activation, and that posttranslational ADPRT-mediated modification of the inflammasome is a newly discovered mechanism for inflammasome activation with subsequent release of IL-1β and associated pathologies.