Background Lipopolysaccharide (LPS) often presents in high concentrations in particulate matter (PM), few studies have reported the enhancing effects of both LPS and PM on airway inflammation in mice and the role of toll-like receptors (TLRs) in this process. Asian sand dust (ASD) is observed most frequently during the spring. This study aimed to clarify the role of TLRs in murine lung eosinophilia exacerbated by ASD and LPS. Methods The effects of LPS and ASD co-treatment on ovalbumin (OVA)-induced lung eosinophilia were investigated using wild-type (WT), TLR2-/-, TLR4-/-, and adaptor protein myeloid differentiation factor 88 (MyD88)-/- BALB/c mice. ASD was heated (H-ASD) to remove the toxic organic substances. WT, TLR2-/-, TLR4-/- and MyD88-/- BALB/c mice were intratracheally instilled with four different combinations of LPS, H-ASD and OVA treatment. Subsequently, the pathological changes in lungs, immune cell profiles in bronchoalveolar lavage fluid (BALF), inflammatory cytokines/chemokines levels in BALF and OVA-specific immunoglobulin (Ig) in serum were analyzed. Results In WT mice, H-ASD + LPS exacerbated OVA-induced lung eosinophilia. This combination of treatments increased the proportion of eosinophils and the levels of IL-5, IL-13, eotaxin in BALF, as well as the production of OVA-specific IgE and IgG1 in serum compared to OVA treatment alone. Although these effects were stronger in TLR2-/- mice than in TLR4-/- mice, the expression levels of IL-5, IL-13, eotaxin were somewhat increased in TLR4-/- mice treated with OVA + H-ASD + LPS. In MyD88-/- mice, this pro-inflammatory mediator-induced airway inflammation was considerably weak and the pathological changes in lungs were negligible. Conclusions These results suggest that LPS and H-ASD activate OVA-induced Th2 response in mice, and exacerbate lung eosinophilia via TLR4/MyD88, TLR4/TRIF and other TLR4-independent pathways.

中文翻译：

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脂多糖和沙漠尘埃的共同暴露通过 TLR4/MyD88 依赖性和非依赖性途径导致小鼠卵清蛋白诱导的过敏性肺部炎症恶化。

背景脂多糖 (LPS) 通常以高浓度存在于颗粒物 (PM) 中，很少有研究报道 LPS 和 PM 对小鼠气道炎症的增强作用以及 Toll 样受体 (TLR) 在此过程中的作用。亚洲沙尘 (ASD) 在春季最常见。本研究旨在阐明 TLR 在 ASD 和 LPS 加重的小鼠肺嗜酸性粒细胞增多中的作用。方法 使用野生型 (WT)、TLR2-/-、TLR4-/- 和衔接蛋白骨髓分化因子 88 (MyD88)- 研究 LPS 和 ASD 联合治疗对卵清蛋白 (OVA) 诱导的肺嗜酸性粒细胞增多的影响/- BALB/c 小鼠。加热 ASD (H-ASD) 以去除有毒有机物质。将 WT、TLR2-/-、TLR4-/- 和 MyD88-/- BALB/c 小鼠气管内灌输四种不同的 LPS 组合，H-ASD 和 OVA 治疗。随后，分析了肺的病理变化、支气管肺泡灌洗液（BALF）中的免疫细胞谱、BALF中的炎性细胞因子/趋化因子水平和血清中的OVA特异性免疫球蛋白（Ig）。结果 在 WT 小鼠中，H-ASD + LPS 加剧了 OVA 诱导的肺嗜酸性粒细胞增多。与单独的 OVA 治疗相比，这种治疗组合增加了 BALF 中嗜酸性粒细胞的比例和 IL-5、IL-13、eotaxin 的水平，以及血清中 OVA 特异性 IgE 和 IgG1 的产生。尽管这些作用在 TLR2-/- 小鼠中比在 TLR4-/- 小鼠中更强，但在用 OVA + H-ASD + LPS 处理的 TLR4-/- 小鼠中，IL-5、IL-13、eotaxin 的表达水平有所增加. 在 MyD88-/- 小鼠中，这种促炎介质引起的气道炎症相当弱，肺部的病理变化可以忽略不计。结论 这些结果表明 LPS 和 H-ASD 在小鼠中激活 OVA 诱导的 Th2 反应，并通过 TLR4/MyD88、TLR4/TRIF 和其他 TLR4 非依赖性途径加剧肺嗜酸性粒细胞增多。