Eosinophils are important for protection, immunoregulation and pathology during infection with nematode microfilariae.
Eosinophils are important for protection, immunoregulation and pathology during infection with nematode microfilariae.
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DOI：
10.1371/journal.ppat.1003988
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发表时间：
2014-03
期刊：
影响因子：
6.7
通讯作者：
Lawrence RA
中科院分区：
文献类型：
--
作者：
Cadman ET;Thysse KA;Bearder S;Cheung AY;Johnston AC;Lee JJ;Lawrence RA
嗜酸性粒细胞反应是过敏性和寄生虫病的典型表现。在蠕虫病中，嗜酸性粒细胞在免疫反应中具有保护作用，在病理反应中具有破坏作用。为了研究嗜酸性粒细胞在丝虫病感染过程中是否参与保护和病理作用，我们研究了嗜酸性粒细胞及其颗粒蛋白、嗜酸性过氧化物酶（EPO）和主要碱性蛋白-1 （MBP-1）在马来布鲁氏微丝虫病感染过程中的作用。利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原发性感染中清除微丝虫病中的作用，而不是体内的挑战感染。单独删除EPO或MBP-1不足以消除寄生虫清除，这表明要么这些分子是多余的，要么嗜酸性粒细胞通过增强其他保护性反应间接作用于寄生虫清除。嗜酸性粒细胞的缺失增加了肥大细胞的募集，而不是其他类型的细胞，在攻击感染期间进入支气管肺泡灌洗液。除了嗜酸性粒细胞或EPO单独缺失外，通过ELISA检测，寄生虫诱导的IgE反应增强，表明嗜酸性粒细胞参与了IgE的调节。全身容积描记显示，在缺乏嗜酸性粒细胞的攻毒感染中，线虫诱导的气道生理变化减少，而在单纯缺乏EPO的原发性感染中，线虫诱导的气道生理变化也减少。然而，缺乏嗜酸性粒细胞或MBP-1实际上增加了杯状细胞粘液的产生。我们没有发现在缺乏嗜酸性粒细胞、EPO或MBP-1的情况下，细胞因子反应有任何重大差异。这些结果表明，在线虫诱导的病理过程中，嗜酸性粒细胞通过颗粒分泌积极参与IgE和杯状细胞粘液产生的调节，并强调了它们作为效应细胞、损伤诱导细胞和形成先天和适应性免疫的监督细胞的重要性。嗜酸性粒细胞募集是变态反应性和寄生性蠕虫病的典型特征。阐明嗜酸性粒细胞在这些疾病中的作用对于理解其保护机制和病理发展具有关键意义。在过去的几年里，嗜酸性粒细胞在蠕虫防御中所起的作用已被使用体内模型解剖，它们在保护中的重要性已被证明对宿主-寄生虫组合具有高度特异性。本研究剖析了嗜酸性粒细胞在感染人淋巴丝虫病中的作用，马来亚布鲁吉原虫，它引起了主要被忽视的热带病淋巴丝虫病。特别地，我们研究了嗜酸性粒细胞在产生保护和病理两方面的双刃剑作用。我们明确地证实了嗜酸性粒细胞对马来芽孢杆菌微丝虫病的保护作用，并表明这种保护作用不是由嗜酸性粒细胞颗粒蛋白、主要碱性蛋白或嗜酸性粒细胞过氧化物酶单独释放介导的。总的来说，我们发现在感染马来芽孢杆菌微丝虫期间，嗜酸性粒细胞对初级保护反应至关重要。然而，嗜酸性粒细胞有助于线虫诱导的肺功能障碍，此外，嗜酸性粒细胞颗粒是寄生虫诱导的肺部炎症和一些适应性免疫反应的重要负调节因子。
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. Eosinophil recruitment is a classic characteristic of both allergic and parasitic helminth diseases. Elucidation of the role of eosinophils in these diseases is of pivotal importance for understanding the mechanisms of protection and the development of pathology. In the last few years, the part played by eosinophils in helminth-defence has been dissected using in vivo models and their importance in protection has been shown to be highly specific to the host-parasite combination. This study dissects the role of eosinophils during infection with the human lymphatic filarial parasite, Brugia malayi, which causes the major neglected tropical disease, lymphatic filariasis. In particular, we study the role of the eosinophil as a double–edged sword in generating both protection and pathology. We definitively confirm the importance of eosinophils in protection against B. malayi microfilariae and show that protection is not mediated by release of the eosinophil granule proteins, major basic protein or eosinophil peroxidase alone. Overall, we reveal that during an infection with B. malayi microfilariae, eosinophils are critical for primary protective responses. However, eosinophils contribute to nematode-induced lung dysfunction, while additionally, eosinophil granules are important negative regulators of parasite-induced lung inflammatory and some adaptive immune responses.
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影响因子：
15.3
作者：
Jacobsen, Elizabeth A.;Ochkur, Sergei I.;Pero, Ralph S.;Taranova, Anna G.;Protheroe, Cheryl A.;Colbert, Dana C.;Lee, Nancy A.;Lee, James J.
通讯作者：
Lee, James J.
影响因子：
4.4
作者：
Fabre, Valeria;Beiting, Daniel P.;Appleton, Judith A.
通讯作者：
Appleton, Judith A.
影响因子：
--
作者：
Lomask, Morton
通讯作者：
Lomask, Morton
影响因子：
20.3
作者：
Doyle, Alfred D.;Jacobsen, Elizabeth A.;Lee, Nancy A.
通讯作者：
Lee, Nancy A.
DOI：
10.1073/pnas.0607863103
发表时间：
2006-10-31
影响因子：
11.1
作者：
Fulkerson, Patricia C.;Fischetti, Christine A.;Rothenberg, Marc E.
通讯作者：
Rothenberg, Marc E.