Institute of Environmental Medicine, Division of Molecular Toxicology, Karolinska Institutet, Stockholm, Sweden.
Part Fibre Toxicol. 2012 May 23;9:16. doi: 10.1186/1743-8977-9-16.
Single-walled carbon nanotubes (SWCNT) trigger pronounced inflammation and fibrosis in the lungs of mice following administration via pharyngeal aspiration or inhalation. Human exposure to SWCNT in an occupational setting may occur in conjunction with infections and this could yield enhanced or suppressed responses to the offending agent. Here, we studied whether the sequential exposure to SWCNT via pharyngeal aspiration and infection of mice with the ubiquitous intracellular parasite Toxoplasma gondii would impact on the immune response of the host against the parasite.
C57BL/6 mice were pre-exposed by pharyngeal administration of SWCNT (80 + 80 μg/mouse) for two consecutive days followed by intravenous injection with either 1x103 or 1x104 green fluorescence protein and luciferase-expressing T. gondii tachyzoites. The dissemination of T. gondii was monitored by in vivo bioluminescence imaging in real time for 7 days and by plaque formation. The inflammatory response was analysed in bronchoalveolar lavage (BAL) fluid, and by assessment of morphological changes and immune responses in lung and spleen.
There were no differences in parasite distribution between mice only inoculated with T. gondii or those mice pre-exposed for 2 days to SWCNT before parasite inoculum. Lung and spleen histology and inflammation markers in BAL fluid reflected the effects of SWCNT exposure and T. gondii injection, respectively. We also noted that CD11c positive dendritic cells but not F4/80 positive macrophages retained SWCNT in the lungs 9 days after pharyngeal aspiration. However, co-localization of T. gondii with CD11c or F4/80 positive cells could not be observed in lungs or spleen. Pre-exposure to SWCNT did not affect the splenocyte response to T. gondii.
Taken together, our data indicate that pre-exposure to SWCNT does not enhance or suppress the early immune response to T. gondii in mice.
经口吸入或吸入途径给予单壁碳纳米管（SWCNT）后，可在小鼠肺部引发明显的炎症和纤维化。人类在职业环境中接触 SWCNT 时，可能同时伴有感染，这可能会导致对致病剂的反应增强或抑制。在这里，我们研究了通过经口吸入途径连续暴露于 SWCNT 并感染常见的细胞内寄生虫刚地弓形虫，是否会影响宿主对寄生虫的免疫反应。
C57BL/6 小鼠连续两天经口给予 SWCNT（80+80μg/只）预暴露，然后静脉注射 1x103 或 1x104 个表达绿色荧光蛋白和荧光素酶的刚地弓形虫速殖子。通过实时体内生物发光成像监测刚地弓形虫的传播，持续 7 天，并通过噬菌斑形成进行监测。通过支气管肺泡灌洗液（BAL）分析炎症反应，并通过评估肺和脾的形态变化和免疫反应进行分析。
仅接种刚地弓形虫或在接种寄生虫前 2 天经口给予 SWCNT 预暴露的小鼠之间，寄生虫的分布没有差异。肺和脾组织学以及 BAL 液中的炎症标志物反映了 SWCNT 暴露和刚地弓形虫注射的影响。我们还注意到，在经口吸入后 9 天，CD11c 阳性树突状细胞而非 F4/80 阳性巨噬细胞在肺部保留了 SWCNT。然而，在肺或脾中均未观察到刚地弓形虫与 CD11c 或 F4/80 阳性细胞的共定位。SWCNT 预暴露不影响脾细胞对刚地弓形虫的反应。
总的来说，我们的数据表明，SWCNT 预暴露不会增强或抑制小鼠对刚地弓形虫的早期免疫反应。
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