The influence of smoke- or air pollution-derived cytoplasmic particulate matter (PM) can be detrimental and lead to failed lung immunity. We investigated mycobacterial uptake, intracellular replication, and soluble immune mediator responses of human bronchoalveolar lavage cells (BALC) loaded with/without PM, to infection with mycobacterial strains. We observed that only BALC containing PM display an ex vivo phenotypic profile dominated by spontaneous interleukin (IL) -10 production. PM loaded BALC retained the ability to phagocytose both Mycobacterium bovis Bacille Calmette Guérin (BCG) and Mycobacterium tuberculosis (M.tb) ΔleuDΔpanCD at equal efficacy as clear non-PM loaded BALC. However, immune responsiveness, such as the production of IL-6 (p=0.015) and tumor necrosis factor (TNF)-α (p= 0.0172) immediately post M.bovis BCG infection, were dramatically lower in black BALC loaded with PM versus clear non-PM loaded BALC. By 24 hour post infection, differential immune responses to M.bovis BCG between black versus clear BALC waned, and instead, production of IL-6 (p= 0.03) and IL-1α (p= 0.04 ) by black BALC were lower versus clear BALC following M.tb ΔleuDΔpanCD infection. Considering that TNFα and IL-6 are characterized as critical to host protection against mycobacteria, our findings suggest that BALC loaded with inhaled PM, display lower levels of anti-mycobacterial mediators, and that the response magnitude differs according to infective mycobacterial strain. Even though this did not translate into altered mycobacterial killing at early time points post infection, the long-term impact of such changes remains to be established.

中文翻译：

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吸入颗粒物影响人肺吞噬细胞对分枝杆菌的免疫反应

烟雾或空气污染衍生的细胞质颗粒物 (PM) 的影响可能是有害的，并导致肺免疫失败。我们研究了负载/不负载 PM 的人支气管肺泡灌洗细胞 (BALC) 对分枝杆菌菌株感染的分枝杆菌摄取、细胞内复制和可溶性免疫介质反应。我们观察到只有含有 PM 的 BALC 显示出以自发白细胞介素 (IL) -10 产生为主的离体表型谱。负载 PM 的 BALC 保留了吞噬牛分枝杆菌 Bacille Calmette Guérin (BCG) 和结核分枝杆菌 (M.tb) ΔleuDΔpanCD 的能力，其功效与不含 PM 的透明 BALC 相同。然而，免疫反应，例如在感染牛支原体 BCG 后立即产生 IL-6 (p=0.015) 和肿瘤坏死因子 (TNF)-α (p= 0.0172)，与不含 PM 的透明 BALC 相比，负载 PM 的黑色 BALC 显着降低。到感染后 24 小时，黑色与透明 BALC 对牛支原体 BCG 的差异免疫反应减弱，相反，黑色 BALC 产生的 IL-6 (p= 0.03) 和 IL-1α (p= 0.04) 低于透明M.tb ΔleuDΔpanCD 感染后的 BALC。考虑到 TNFα 和 IL-6 被表征为对宿主保护免受分枝杆菌至关重要，我们的研究结果表明，负载吸入 PM 的 BALC 显示出较低水平的抗分枝杆菌介质，并且响应幅度因感染性分枝杆菌菌株而异。尽管这并没有转化为感染后早期分枝杆菌杀灭的改变，但这种变化的长期影响仍有待确定。