Requirement of interleukin-17A for systemic anti-Candida albicans host defense in mice
Requirement of interleukin-17A for systemic anti-Candida albicans host defense in mice
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DOI：
10.1086/422329
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发表时间：
2004-08-01
影响因子：
6.4
通讯作者：
Schwarzenberger, P
中科院分区：
文献类型：
--
作者：
Huang, WT;Na, L;Schwarzenberger, P
T细胞是正常的宿主防御真菌感染所必需的，患有T细胞缺乏综合征的个体对真菌病原体高度易感。白细胞介素（IL）-17 A是一种促炎细胞因子，其使骨髓和淋巴宿主防御相互关联。在系统性念珠菌病的鼠模型中评价鼠（m）IL-17 A/mIL-17 A受体（R）相互作用的作用。响应于用白色念珠菌的系统性攻击，诱导mIL-17 A的表达，并且IL-17 AR敲除（IL-17 AR（-/-））小鼠具有剂量依赖性的、显著降低的存活率。IL-17 AR（-/-）小鼠肾脏中的真菌负荷显著增加（96 h时为25倍）。在IL-17 AR（-/-）小鼠中，外周中性粒细胞的动员及其向感染器官的流入均显著受损和延迟。mIL-17 A的体内表达可保护正常小鼠免受致死剂量的C.白色念珠菌（第7天100%，第42天65%）。这些数据表明，mIL-17 A/mIL-17 AR系统是体内正常真菌宿主防御所必需的。IL-17 A可能具有作为系统性C.免疫功能低下的癌症患者或晚期获得性免疫缺陷综合征患者的白色念珠菌感染。
T cells are required for normal host defense against fungal infection, and individuals with T cell - deficiency syndromes are highly susceptible to fungal pathogens. Interleukin (IL)-17A is a proinflammatory cytokine that interconnects myeloid and lymphoid host defense. The role of murine ( m) IL-17A/mIL-17A receptor ( R) interactions was evaluated in a murine model of systemic candidiasis. In response to systemic challenge with Candida albicans, expression of mIL-17A was induced, and IL-17AR knockout ( IL-17AR(-/-)) mice had dose-dependent, substantially reduced survival. Fungal burden in the kidneys of IL-17AR(-/-) mice was dramatically increased (25-fold at 96 h). In IL-17AR(-/-) mice, both mobilization of peripheral neutrophils and their influx to infected organs were significantly impaired and delayed. In vivo expression of mIL-17A protected normal mice from a lethal dose of C. albicans (100% at day 7 and 65% at day 42). The data suggest that the mIL-17A/mIL-17AR system is required for normal fungal host defense in vivo. IL-17A could have potential as a therapeutic cytokine for systemic C. albicans infections in immunocompromised patients with cancer or advanced acquired immunodeficiency syndrome.