Single-Cell RNA Sequencing Reveals a Unique Monocyte Population in Bronchoalveolar Lavage Cells of Mice Challenged With Afghanistan Particulate Matter and Allergen
Single-Cell RNA Sequencing Reveals a Unique Monocyte Population in Bronchoalveolar Lavage Cells of Mice Challenged With Afghanistan Particulate Matter and Allergen
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DOI：
10.1093/toxsci/kfab065
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发表时间：
2021-05-29
影响因子：
3.8
通讯作者：
Day, Brian J.
中科院分区：
文献类型：
--
作者：
Berman, Reena;Min, Elysia;Day, Brian J.
从阿富汗部署返回后，大量美国军事人员报告出现与部署相关的肺部疾病 (DRLD) 症状，包括与哮喘样气道疾病相符的症状。 DRLD 被认为是由长期吸入有毒的沙漠颗粒物引起的，这种颗粒物可能在部署后的环境中持续存在，例如暴露于常见的家庭过敏原。本研究的目的是确定暴露于阿富汗沙漠颗粒物 (APM) 和屋尘螨 (HDM) 的小鼠肺白细胞的转录组反应。 C57BL/6 小鼠（n = 15/组）暴露于过滤空气或雾化 APM 中 12 天，然后鼻内 PBS 或 HDM 过敏原激发 24 小时。收集支气管肺泡灌洗 (BAL) 细胞用于单细胞 RNA 测序 (scRNAseq)，并评估炎症和气道高反应性。 BAL 细胞 scRNAseq 数据的无监督聚类揭示了仅由 APM 和过敏原治疗诱导的独特单核细胞群。该单核细胞群的特点是表达与过敏性哮喘相关的基因，包括 Alox15。我们通过肺组织免疫染色验证了单核细胞中 Alox15 的表达。与过滤空气对照相比，APM 预暴露以及随后的 HDM 挑战导致呼吸系统总阻力显着增加。使用该小鼠模型来模拟 DRLD，我们证明在部署期间吸入空气中的 PM 可能会促使气道在回家后对过敏原暴露更加敏感，这可能与免疫反应失调有关，例如诱导独特的肺单核细胞群。
Upon returning from deployment to Afghanistan, a substantial number of U.S. military personnel report deploymentrelated lung disease (DRLD) symptoms, including those consistent with an asthma-like airways disease. DRLD is thought to be caused by prolonged inhalation of toxic desert particulate matter, which can persist in the postdeployment setting such as exposure to common household allergens. The goal of this study was to define the transcriptomic responses of lung leukocytes of mice exposed to Afghanistan desert particulate matter (APM) and house dust mite (HDM). C57BL/6 mice (n = 15/group) were exposed to filtered air or aerosolized APM for 12 days, followed by intranasal PBS or HDM allergen challenges for 24 h. Bronchoalveolar lavage (BAL) cells were collected for single-cell RNA sequencing (scRNAseq), and assessment of inflammation and airway hyper-responsiveness. Unsupervised clustering of BAL cell scRNAseq data revealed a unique monocyte population induced only by both APM and allergen treatments. This population of monocytes is characterized by the expression of genes involved in allergic asthma, including Alox15. We validated Alox15 expression in monocytes via immunostaining of lung tissue. APM pre-exposure, followed by the HDM challenge, led to significantly increased total respiratory system resistance compared with filtered air controls. Using this mouse model to mimic DRLD, we demonstrated that inhalation of airborne PM during deployment may prime airways to be more responsive to allergen exposure after returning home, which may be linked to dysregulated immune responses such as induction of a unique lung monocyte population.