Cadman Emma T, Thysse Katherine A, Bearder Siobhan, Cheung Anita Y N, Johnston Ashleigh C, Lee James J, Lawrence Rachel A
The Royal Veterinary College, Department of Comparative Biomedical Sciences, London, United Kingdom.
Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, Arizona, United States of America.
PLoS Pathog. 2014 Mar 13;10(3):e1003988. doi: 10.1371/journal.ppat.1003988. eCollection 2014 Mar.
Eosinophil responses typify both allergic and parasitic helminth disease. In helminthic disease, the role of eosinophils can be both protective in immune responses and destructive in pathological responses. To investigate whether eosinophils are involved in both protection and pathology during filarial nematode infection, we explored the role of eosinophils and their granule proteins, eosinophil peroxidase (EPO) and major basic protein-1 (MBP-1), during infection with Brugia malayi microfilariae. Using eosinophil-deficient mice (PHIL), we further clarify the role of eosinophils in clearance of microfilariae during primary, but not challenge infection in vivo. Deletion of EPO or MBP-1 alone was insufficient to abrogate parasite clearance suggesting that either these molecules are redundant or eosinophils act indirectly in parasite clearance via augmentation of other protective responses. Absence of eosinophils increased mast cell recruitment, but not other cell types, into the broncho-alveolar lavage fluid during challenge infection. In addition absence of eosinophils or EPO alone, augmented parasite-induced IgE responses, as measured by ELISA, demonstrating that eosinophils are involved in regulation of IgE. Whole body plethysmography indicated that nematode-induced changes in airway physiology were reduced in challenge infection in the absence of eosinophils and also during primary infection in the absence of EPO alone. However lack of eosinophils or MBP-1 actually increased goblet cell mucus production. We did not find any major differences in cytokine responses in the absence of eosinophils, EPO or MBP-1. These results reveal that eosinophils actively participate in regulation of IgE and goblet cell mucus production via granule secretion during nematode-induced pathology and highlight their importance both as effector cells, as damage-inducing cells and as supervisory cells that shape both innate and adaptive immunity.
嗜酸性粒细胞反应是过敏性疾病和寄生虫性蠕虫病的典型特征。在蠕虫病中，嗜酸性粒细胞在免疫反应中具有保护作用，而在病理反应中则具有破坏作用。为了研究嗜酸性粒细胞在丝虫线虫感染过程中是否参与保护和病理过程，我们探讨了嗜酸性粒细胞及其颗粒蛋白、嗜酸性粒细胞过氧化物酶（EPO）和主要碱性蛋白-1（MBP-1）在马来布鲁线虫微丝蚴感染过程中的作用。使用嗜酸性粒细胞缺陷小鼠（PHIL），我们进一步阐明了嗜酸性粒细胞在体内初次感染而非再次感染期间清除微丝蚴中的作用。单独缺失EPO或MBP-1不足以消除寄生虫清除，这表明这些分子要么是冗余的，要么嗜酸性粒细胞通过增强其他保护反应间接参与寄生虫清除。在再次感染期间，嗜酸性粒细胞的缺失增加了肥大细胞向支气管肺泡灌洗液中的募集，但未增加其他细胞类型。此外，单独缺失嗜酸性粒细胞或EPO会增强寄生虫诱导的IgE反应，通过ELISA检测表明嗜酸性粒细胞参与IgE的调节。全身体积描记法表明，在没有嗜酸性粒细胞的再次感染以及仅在没有EPO的初次感染期间，线虫诱导的气道生理变化有所减少。然而，缺乏嗜酸性粒细胞或MBP-1实际上增加了杯状细胞黏液的产生。在没有嗜酸性粒细胞、EPO或MBP-1的情况下，我们未发现细胞因子反应有任何重大差异。这些结果表明，嗜酸性粒细胞在由线虫诱导的病理过程中通过颗粒分泌积极参与IgE和杯状细胞黏液产生的调节，并突出了它们作为效应细胞、损伤诱导细胞以及塑造固有免疫和适应性免疫的监督细胞的重要性。
