Pulmonary Pathogenesis and Immunotoxicology Laboratory, Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0056, USA.
Int J Mol Sci. 2024 Feb 8;25(4):2058. doi: 10.3390/ijms25042058.
(MI) colonizing metalworking fluids (MWFs) has been associated with chronic hypersensitivity pneumonitis (HP) in machinists. However, it is etiologically unclear why only certain mycobacteria-contaminated fluids induce this interstitial lung disease. We hypothesized that this may be due to differential immunogenicity and the HP-inducing potential of MI strains/genotypes as well as the confounding effect of co-inhaled endotoxin-producers. To test this hypothesis, we optimized a chronic HP mouse model in terms of MI antigen dose, timepoint of sacrifice, and form of antigen (cell lysates vs. live cells) and compared six different field-isolated MI strains. Overall, MJY10 was identified as the most immunogenic and MJY4 (or MJY13) as the least immunogenic genotype based on lung pathoimmunological changes as well as Th1 cellular response (IFN-γ release). Infection with MI live cells induced a more severe phenotype than MI cell lysate. Co-exposure with caused a greater degree of lung innate immune response and granuloma formation but a diminished adaptive (Th1) immune response (IFN-γ) in the lung and spleen. In summary, this study led to the first demonstration of differential immunogenicity and the disease-inducing potential of field strains of MI and an interfering effect of the co-contaminating Pseudomonas. The improved chronic MI-HP mouse model and the identified polar pair of MI strains will facilitate future diagnostic and therapeutic research on this poorly understood environmental lung disease.
（米）定植于金属加工液（MWFs）与机加工人员的慢性过敏性肺炎（HP）有关。然而，尚不清楚为什么只有某些分枝杆菌污染的液体才会引发这种间质性肺病。我们假设这可能是由于 MI 菌株/基因型的差异免疫原性和 HP 诱导潜力，以及共吸入内毒素产生菌的混杂作用。为了验证这一假设，我们优化了慢性 HP 小鼠模型的 MI 抗原剂量、牺牲时间点和抗原形式（细胞裂解物与活细胞），并比较了六种不同的野外分离 MI 菌株。总体而言，MJY10 被确定为最具免疫原性的菌株，而 MJY4（或 MJY13）则是免疫原性最低的基因型，这是基于肺部病理免疫学变化以及 Th1 细胞反应（IFN-γ 释放）得出的。感染 MI 活细胞比 MI 细胞裂解物诱导出更严重的表型。与共同暴露会导致肺部固有免疫反应和肉芽肿形成程度更大，但肺部和脾脏中的适应性（Th1）免疫反应（IFN-γ）减弱。总之，这项研究首次证明了 MI 野外分离株的差异免疫原性和疾病诱导潜力，以及共污染假单胞菌的干扰作用。改进的慢性 MI-HP 小鼠模型和确定的 MI 极性菌株对这种了解甚少的环境性肺部疾病的未来诊断和治疗研究将有所帮助。
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