Department of Dermatology, Research Center of Medical Mycology, Peking University First Hospital, Peking University, Beijing, China.
Med Mycol. 2010 Mar;48(2):303-9. doi: 10.1080/13693780903136887.
Aspergillus fumigatus is an important opportunistic fungal pathogen. Patients treated with chemotherapeutic agent such as cyclophosphamide are susceptible to invasive pulmonary aspergillosis. Dectin-1 is a pattern recognition receptor critically involved in immune responses to A. fumigatus. Therefore, we tested whether cyclophosphamide treatment could cause alterations in dectin-1 expression in the lung, which could contribute to invasive pulmonary Aspergillus infections in patients. We established a murine A. fumigatus infectious model to investigate the kinetics of dectin-1 expression in lung tissues in the presence or absence of cyclophosphamide treatment. During infection, dectin-1 expression was strikingly increased in immunocompetent mice infected with A. fumigatus as compared to those in a non-infected control group. In vitro macrophages stimulated with heat-inactivated A. fumigatus conidia expressed a significantly elevated level of dectin-1. Infected mice treated with cyclophosphamide showed decreased levels of dectin-1 and a higher fungal burden in the lung than the infected mice without cyclophosphamide treatment. These results suggest that dectin-1 is involved in host defense against A. fumigatus infection and that suppression of dectin-1 expression caused by cyclophosphamide may contribute to susceptibility to infections caused by this fungus in the immunocompromised host.
烟曲霉是一种重要的机会性真菌病原体。接受化疗药物（如环磷酰胺）治疗的患者易患侵袭性肺曲霉病。Dectin-1 是一种模式识别受体，在对烟曲霉的免疫反应中起着至关重要的作用。因此，我们检测了环磷酰胺治疗是否会导致肺部 dectin-1 表达的改变，这可能导致免疫功能低下宿主发生侵袭性肺曲霉感染。我们建立了烟曲霉感染的小鼠模型，以研究在存在或不存在环磷酰胺治疗的情况下，肺部 dectin-1 表达的动力学。在感染过程中，与未感染对照组相比，免疫功能正常的感染烟曲霉的小鼠肺部 dectin-1 表达显著增加。体外用热灭活烟曲霉分生孢子刺激的巨噬细胞表达明显升高水平的 dectin-1。与未接受环磷酰胺治疗的感染小鼠相比，接受环磷酰胺治疗的感染小鼠肺部的 dectin-1 水平降低，真菌负荷增加。这些结果表明，dectin-1 参与宿主对烟曲霉感染的防御，而环磷酰胺抑制 dectin-1 表达可能导致免疫功能低下宿主对该真菌感染的易感性增加。
