Impairment of alternative macrophage activation delays cutaneous leishmaniasis in nonhealing BALB/c mice
Impairment of alternative macrophage activation delays cutaneous leishmaniasis in nonhealing BALB/c mice
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DOI：
10.4049/jimmunol.176.2.1115
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发表时间：
2006-01-15
影响因子：
4.4
通讯作者：
Brombacher, F
中科院分区：
文献类型：
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作者：
Hölscher, C;Arendse, B;Brombacher, F
IL-4 R α在各种细胞类型上表达，是IL-4和IL-13两种受体的组分。BALB/c小鼠对硕大利什曼原虫的易感性被认为依赖于产生IL-4和IL-13的Th 2细胞的发育，而Th 1细胞分泌IFN-γ与抗性有关。尽管Th 2细胞持续发育，但IL-4 R α缺陷型BALB/c小鼠能够控制急性皮肤利什曼病，这表明IL-4 R α携带细胞而非Th 2细胞有助于易感性。为了分析IL-4 Ra对巨噬细胞的作用，将最近产生的具有易感性BALB/c遗传背景的巨噬细胞/嗜中性粒细胞特异性IL-4 Ra缺陷小鼠感染L.少校引人注目的是，巨噬细胞/嗜利什曼细胞特异性IL-4 Ra缺陷小鼠显示出显著延迟的疾病进展，具有正常的Th 2和2型Ab应答，但改善了巨噬细胞杀利什曼效应子功能并降低了抗利什曼酶活性。总之，这些结果表明，替代巨噬细胞活化有助于皮肤利什曼病的易感性。
Expressed on various cell types, the IL-4R alpha is a component of both receptors for IL-4 and IL-13. Susceptibility of BALB/c mice to Leishmania major is believed to be dependent on the development of IL-4- and IL-13-producing Th2 cells, while IFN-gamma secretion by Th1 cells is related to resistance. Despite a sustained development of Th2 cells, IL-4R alpha-deficient BALB/c mice are able to control acute cutaneous leishmaniasis, suggesting that IL-4R alpha-bearing cells other than Th2 cells contribute to susceptibility. To analyze the contribution of the IL-4Ra on macrophages, recently generated macrophage/neutrophil-specific IL-4Ra-deficient mice on a susceptible BALB/c genetic background were infected with L. major. Strikingly, macrophage/neutrophil-specific IL-4Ra-deficient mice showed a significantly delayed disease progression with normal Th2 and type 2 Ab responses but improved macrophage leishmanicidal effector functions and reduced arginase activity. Together, these results suggest that alternative macrophage activation contributes to susceptibility in cutaneous leishmaniasis.