Schelenz S, Smith D A, Bancroft G J
Department of Microbiology, Guy's, King's and St Thomas's School of Medicine, London, UK.
Med Mycol. 1999 Jun;37(3):183-94. doi: 10.1046/j.1365-280x.1999.00219.x.
Aspergillus fumigatus causes life-threatening invasive pulmonary aspergillosis in the immunocompromised patient. In this study we have used a murine model of intratracheal challenge with A. fumigatus to investigate the recruitment of inflammatory cells in the lung and the expression of proinflammatory cytokines and chemokines. Our results show that A. fumigatus causes an acute pulmonary inflammatory response which is dominated by neutrophils and to a lesser extent macrophages. During the peak of infection, proinflammatory cytokines (TNF-alpha, GM-CSF and IL-1beta) and chemokines (MIP-1alpha, MCP-1 and MIP-2), are induced within the lung. Furthermore, treatment of mice with neutralizing anti-TNF-alpha and anti-GM-CSF mAbs reduced the influx of neutrophils into the lung and delayed fungal clearance. Our observations show that Aspergillus conidia are effective inducers of host chemokine responses both in vitro and in vivo. Furthermore, TNF-alpha and GM-CSF play a central role in the recruitment of neutrophils into the lung in response to this clinically important pathogen.
烟曲霉可在免疫功能低下的患者中引发危及生命的侵袭性肺曲霉病。在本研究中，我们使用了气管内接种烟曲霉的小鼠模型，以研究肺部炎症细胞的募集以及促炎细胞因子和趋化因子的表达。我们的结果表明，烟曲霉会引发急性肺部炎症反应，该反应以中性粒细胞为主，巨噬细胞参与程度较低。在感染高峰期，肺部会诱导促炎细胞因子（肿瘤坏死因子-α、粒细胞-巨噬细胞集落刺激因子和白细胞介素-1β）和趋化因子（巨噬细胞炎性蛋白-1α、单核细胞趋化蛋白-1和巨噬细胞炎性蛋白-2）。此外，用中和性抗肿瘤坏死因子-α和抗粒细胞-巨噬细胞集落刺激因子单克隆抗体治疗小鼠，可减少中性粒细胞流入肺部，并延迟真菌清除。我们的观察结果表明，烟曲霉分生孢子在体外和体内均是宿主趋化因子反应的有效诱导剂。此外，肿瘤坏死因子-α和粒细胞-巨噬细胞集落刺激因子在针对这种临床重要病原体的中性粒细胞募集到肺部过程中发挥着核心作用。
