The study of multi-walled carbon nanotube (MWCNT) induced immunotoxicity is crucial for determining hazards posed to human health. MWCNT exposure most commonly occurs via the airways, where macrophages are first line responders. Here we exploit an in vitro assay, measuring dose-dependent secretion of a wide panel of cytokines, as a measure of immunotoxicity following the non-lethal, multi-dose exposure (IC5, IC10 and IC20) to 7 MWCNTs with different intrinsic properties. We find that a tangled structure, and small aspect ratio are key properties predicting MWCNT induced immunotoxicity, mediated predominantly by IL1B cytokine secretion. To assess the mechanism of action giving rise to MWCNT immunotoxicity, transcriptomics analysis was linked to cytokine secretion in a multilayer model established through correlation analysis across exposure concentrations. This reinforced the finding that tangled MWCNTs have greater immunomodulatory potency, displaying enrichment of immune system, signal transduction and pattern recognition associated pathways. Together our results further elucidate how structure, length and aspect ratio, critical intrinsic properties of MWCNTs, are tied to immunotoxicity.

多壁碳纳米管（MWCNT）诱导的免疫毒性的研究对于确定对人类健康造成的危害至关重要。多壁碳纳米管暴露最常通过气道发生，其中巨噬细胞是一线反应者。在这里，我们利用体外测定，测量多种细胞因子的剂量依赖性分泌，作为对具有不同内在特性的 7 个 MWCNT 进行非致命、多剂量暴露（IC5、IC10 和 IC20）后免疫毒性的测量。我们发现，缠结结构和小长宽比是预测 MWCNT 诱导的免疫毒性的关键特性，主要由 IL1B 细胞因子分泌介导。为了评估引起 MWCNT 免疫毒性的作用机制，通过跨暴露浓度的相关分析建立了多层模型，将转录组学分析与细胞因子分泌联系起来。这证实了缠结的多壁碳纳米管具有更大的免疫调节效力，显示出免疫系统、信号转导和模式识别相关途径的富集。我们的研究结果进一步阐明了多壁碳纳米管的结构、长度和长宽比等关键内在特性如何与免疫毒性相关。