Eosinophil Deficiency Compromises Parasite Survival in Chronic Nematode Infection
Eosinophil Deficiency Compromises Parasite Survival in Chronic Nematode Infection
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DOI：
10.4049/jimmunol.182.3.1577
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发表时间：
2009-02-01
影响因子：
4.4
通讯作者：
Appleton, Judith A.
中科院分区：
文献类型：
--
作者：
Fabre, Valeria;Beiting, Daniel P.;Appleton, Judith A.
寄生虫引起的免疫反应与慢性过敏有许多共同特征。嗜酸性粒细胞会导致两种疾病中发生的炎症，并且嗜酸性粒细胞在体外释放的有毒产物可以损害或杀死蠕虫。这些观察结果证实了人们普遍持有的观点，即嗜酸性粒细胞可以保护宿主免受寄生虫侵害。小鼠是旋毛虫的天然宿主，旋毛虫是一种在骨骼肌中造成慢性感染的蠕虫。我们在两种嗜酸性粒细胞谱系被消除的小鼠品系中测试了嗜酸性粒细胞对旋毛虫感染的影响。野生型小鼠受感染的肌肉细胞周围的浸润中嗜酸性粒细胞很明显；然而，在缺乏嗜酸性粒细胞的情况下，旋毛虫肌肉幼虫大量死亡。寄生虫死亡与 IFN-γ 增强和 IL-4 产生减少相关。当用诱导型一氧化氮合酶抑制剂治疗小鼠时，幼虫存活率得到改善，这表明一氧化氮途径在寄生虫清除中发挥着重要作用。因此，线虫感染中嗜酸性粒细胞毒性的长期范例需要重新评估，因为我们的结果表明，嗜酸性粒细胞可能以维持慢性感染并确保蠕虫在宿主群体中存活的方式影响免疫反应。这种机制可能被其他依靠慢性感染生存的寄生虫所利用。免疫学杂志，2009，182：1577-1583。
Immune responses elicited by parasitic worms share many features with those of chronic allergy. Eosinophils contribute to the inflammation that occurs in both types of disease, and helminths can be damaged or killed by toxic products released by eosinophils in vitro. Such observations inform the widely held view that eosinophils protect the host against parasitic worms. The mouse is a natural host for Trichinella spiralis, a worm that establishes chronic infection in skeletal muscle. We tested the influence of eosinophils on T. spiralis infection in two mouse strains in which the eosinophil lineage is ablated. Eosinophils were prominent in infiltrates surrounding infected muscle cells of wild-type mice; however, in the absence of eosinophils T. spiralis muscle larvae died in large numbers. Parasite death correlated with enhanced IFN-gamma and decreased IL-4 production. Larval survival improved when mice were treated with inhibitors of inducible NO synthase, implicating the NO pathway in parasite clearance. Thus, the long-standing paradigm of eosinophil toxicity in nematode infection requires reevaluation, as our results suggest that eosinophils may influence the immune response in a manner that would sustain chronic infection and insure worm survival in the host population. Such a mechanism may be deployed by other parasitic worms that depend upon chronic infection for survival. The Journal of Immunology, 2009, 182: 1577-1583.