Antimicrobial nanomaterials frequently induce inflammatory reactions within lung tissues and prompt apoptosis in lung cells, yielding a paradox due to the inherent anti-inflammatory character of apoptosis. This paradox accentuates the elusive nature of the signaling cascade underlying nanoparticle (NP)-induced pulmonary inflammation. In this study, we unveil the pivotal role of nano-microflora interactions, serving as the crucial instigator in the signaling axis of NP-induced lung inflammation. Employing pulmonary microflora-deficient mice, we provide compelling evidence that a representative antimicrobial nanomaterial, silver (Ag) NPs, triggers substantial motility impairment, disrupts quorum sensing, and incites DNA leakage from pulmonary microflora. Subsequently, the liberated DNA molecules recruit caspase-1, precipitating the release of proinflammatory cytokines and activating N-terminal gasdermin D (GSDMD) to initiate pyroptosis in macrophages. This pyroptotic cascade culminates in the emergence of severe pulmonary inflammation. Our exploration establishes a comprehensive mechanistic axis that interlinks the antimicrobial activity of Ag NPs, perturbations in pulmonary microflora, bacterial DNA release, macrophage pyroptosis, and consequent lung inflammation, which helps to gain an in-depth understanding of the toxic effects triggered by environmental NPs.

中文翻译：

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纳米微生物群相互作用通过焦亡诱导肺部炎症

抗菌纳米材料经常诱发肺组织内的炎症反应并促进肺细胞凋亡，由于细胞凋亡固有的抗炎特性，产生了一个悖论。这一悖论凸显了纳米颗粒（NP）诱导的肺部炎症背后的信号级联的难以捉摸的本质。在这项研究中，我们揭示了纳米微生物群落相互作用的关键作用，作为纳米粒子诱导的肺部炎症信号轴的关键煽动者。通过使用肺部微生物群缺陷小鼠，我们提供了令人信服的证据，证明一种代表性的抗菌纳米材料——银（Ag）纳米粒子，会引发严重的运动障碍，破坏群体感应，并引发肺部微生物群的 DNA 泄漏。随后，释放的 DNA 分子募集 caspase-1，促进促炎细胞因子的释放并激活 N 末端gasdermin D (GSDMD) 以引发巨噬细胞焦亡。这种焦亡级联反应最终导致严重肺部炎症的出现。我们的探索建立了一个全面的机制轴，将银纳米颗粒的抗菌活性、肺部微生物群的扰动、细菌DNA释放、巨噬细胞焦亡和随后的肺部炎症相互联系起来，这有助于深入了解环境纳米颗粒引发的毒性作用。