PDF(Pubmed)
Abstract：
Absent in melanoma 2 (AIM2), a key component of the IFI20X/IFI16 (PYHIN) protein family, is characterized as a DNA sensor to detect cytosolic bacteria and DNA viruses. However, little is known about its immunological role during pathogenic Clostridium perfringens (C. perfringens) infection, an extracellular bacterial pathogen. In a pathogenic C. perfringens gas gangrene model, Aim2-/- mice are more susceptible to pathogenic C. perfringens soft tissue infection, revealing the importance of AIM2 in host protection. Notably, Aim2 deficiency leads to a defect in bacterial killing and clearance. Our in vivo and in vitro findings further establish that inflammasome signaling is impaired in the absence of Aim2 in response to pathogenic C. perfringens. Mechanistically, inflammasome signaling downstream of active AIM2 promotes pathogen control. Importantly, pathogenic C. perfringens-derived genomic DNA triggers inflammasome signaling activation in an AIM2-dependent manner. Thus, these observations uncover a central role for AIM2 in host defense and triggering innate immunity to combat pathogenic C. perfringens infections.
摘要：
黑色素瘤2（AIM2）缺失，IFI20X/IFI16（PYHIN）蛋白家族的关键成分，其特征是作为检测细胞溶质细菌和DNA病毒的DNA传感器。然而,对其在致病性产气荚膜梭菌中的免疫学作用知之甚少(C.产气荚膜)感染，细胞外细菌病原体。在致病性产气荚膜梭菌气体坏疽模型中，Aim2-/-小鼠更容易受到致病性产气荚膜梭菌软组织感染，揭示了AIM2在宿主保护中的重要性。值得注意的是,Aim2缺乏导致细菌杀灭和清除的缺陷。我们的体内和体外发现进一步证实,在不存在Aim2的情况下,炎性小体信号传导受损以响应致病性产气荚膜梭菌。机械上,活性AIM2下游的炎性小体信号促进病原体控制。重要的是,致病性产气荚膜梭菌来源的基因组DNA以AIM2依赖性方式触发炎性体信号激活。因此，这些观察揭示了AIM2在宿主防御和触发先天免疫以对抗致病性产气荚膜梭菌感染中的核心作用。
