Interleukin-4 causes susceptibility to invasive pulmonary aspergillosis through suppression of protective type I responses
Interleukin-4 causes susceptibility to invasive pulmonary aspergillosis through suppression of protective type I responses
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DOI：
10.1086/315142
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发表时间：
1999-12-01
影响因子：
6.4
通讯作者：
Romani, L
中科院分区：
文献类型：
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作者：
Cenci, E;Mencacci, A;Romani, L
烟曲霉是一种机会性真菌病原体，可引起多种过敏性和非过敏性气道疾病。侵袭性肺曲霉菌病 (IPA) 是一种非过敏性、危及免疫功能低下患者生命的疾病。在 IPA 小鼠模型中，使用白细胞介素 (IL)-4 缺陷 (IL-4(-/-)) BALB/c 小鼠来检查 IL-4 在肺部病理学和免疫反应中的作用。 IL-4(-/-)小鼠比野生型小鼠对多次鼻内注射活烟曲霉分生孢子引起的感染具有更强的抵抗力。耐药性与肺部炎症病理减少、辅助性 T (Th)-2 反应受损（包括肺嗜酸性粒细胞增多）和 IL-12 依赖性 Th1 反应相关。相反，当IL-12中和时，IL-12(-/-)和干扰素-γ(-/-)小鼠以及IL-4(-/-)小鼠中出现对宿主有害的抗真菌Th2细胞的发育。这些结果表明，IL-4 通过抑制保护性 Th1 反应而使小鼠易受烟曲霉感染。 IL-4 似乎在真菌引起的过敏性和非过敏性肺部疾病的发病机制中具有独特的作用。
Aspergillus fumigatus, an opportunistic fungal pathogen, causes multiple allergic and nonallergic airway diseases. Invasive pulmonary aspergillosis (IPA) is a nonallergic, life-threatening disease of immunocompromised patients. In a murine model of IPA, interleukin (IL)-4-deficient (IL-4(-/-)) BALB/c mice were used to examine the role of IL-4 in lung pathology and immune responses. IL-4(-/-) mice were more resistant than wild-type mice to infection caused by multiple intranasal injections of viable A. fumigatus conidia. Resistance was associated with decreased lung inflammatory pathology, impaired T helper (Th)-2 responses (including lung eosinophilia), and an IL-12-dependent Th1 response. In contrast, development of host-detrimental antifungal Th2 cells occurred in IL-12(-/-) and interferon-gamma(-/-) mice and in IL-4(-/-) mice when subjected to IL-12 neutralization. These results demonstrate that IL-4 renders mice susceptible to infection with A. fumigatus by inhibition of protective Th1 responses. IL-4 appears to have a distinct role in the pathogenesis of allergic and nonallergic lung diseases caused by the fungus.