IL-4(-/-) mice with lethal Mesocestoides corti infections--reduced Th2 cytokines and alternatively activated macrophages.
IL-4(-/-) mice with lethal Mesocestoides corti infections--reduced Th2 cytokines and alternatively activated macrophages.
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DOI：
10.1111/j.1365-3024.2009.01151.x
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发表时间：
2009-12
影响因子：
2.2
通讯作者：
Abraham D
中科院分区：
文献类型：
--
作者：
O'Connell AE;Kerepesi LA;Vandergrift GL;Herbert DR;VAN Winkle TJ;Hooper DC;Pearce EJ;Abraham D
研究发现，与野生型小鼠相比，IL-4 - / -小鼠具有更高的寄生虫负担，因此对入侵重要器官的中介体（Mesocestoides corti）的保护依赖于IL-4的产生。本研究的目的是探讨IL-4在对M. corti的免疫中的作用，重点是免疫学特征和潜在的病理介质。感染M. corti的IL-4 - / -小鼠在32天内死亡率为100%，而野生型小鼠存活约1年。IL-4 - / -小鼠的肝脏、腹膜和胸腔中的寄生虫负荷显著增加，这与炎症细胞募集受损以及单核细胞和巨噬细胞减少有关。与野生型小鼠相比，感染IL-4−/−小鼠脾细胞产生IL-5和肝组织表达IL-5降低。相比之下，IL-4−/−小鼠产生的IFNγ和TNFα量增加。可选择性活化的巨噬细胞是野生型小鼠肝脏肉芽肿的主要特征，精氨酸酶I的表达证明了这一点，而感染IL-4 - / -小鼠的肝脏显示可选择性巨噬细胞活化受损，但经典巨噬细胞活化未增加。因此，IL-4−/−小鼠感染M. corti时的致病性与Th2细胞因子的减少、Th1细胞因子的增加和选择性活化巨噬细胞的损伤有关。
Protection against Mesocestoides corti, a cestode that invades vital organs, is dependent on the production of IL-4, as IL-4−/− mice were found to have higher parasite burdens when compared with wild-type mice. The goal of this study was to investigate the role of IL-4 in immunity to M. corti, focusing on the immunological profile and on potential mediators of pathology. IL-4−/− mice infected with M. corti showed 100% mortality by 32 days, whereas wild-type mice survived for approximately 1 year. Parasite burdens were significantly increased in the liver, peritoneal, and thoracic cavities of IL-4−/− mice, associated with impaired recruitment of inflammatory cells and a reduction in monocytes and macrophages. IL-5 production by splenocytes and expression in liver tissue was decreased in infected IL-4−/− mice compared with wild-type mice. In contrast, IL-4−/− mice produced increased amounts of IFNγ and TNFα. Alternatively activated macrophages were a major feature of liver granulomas in wild-type mice evidenced by Arginase I expression, while livers from infected IL-4−/− mice showed impaired alternative macrophage activation without increased classical macrophage activation. Thus, lethality during M. corti infection of IL-4−/− mice is associated with decreased Th2 cytokines, increased Th1 cytokines and impairment of alternatively activated macrophages.
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DOI：
10.1084/jem.176.1.287
发表时间：
1992-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Stein M;Keshav S;Harris N;Gordon S
通讯作者：
Gordon S
影响因子：
3.1
作者：
Patton, EA;Brunet, LR;Pearce, EJ
通讯作者：
Pearce, EJ
影响因子：
2.2
作者：
Rawat, J;Dixon, JB;Taylor, MJ
通讯作者：
Taylor, MJ
影响因子：
3.1
作者：
Donnelly, S;O'Neill, SM;Dalton, JP
通讯作者：
Dalton, JP
影响因子：
3.1
作者：
Patton, EA;La Flamme, AC;Pearce, EJ
通讯作者：
Pearce, EJ