Department of Medicine, Roswell Park Cancer Institute, School of Medicine and Biomedical Sciences, University of Buffalo, Buffalo, New York 14263, USA.
Curr Opin Pulm Med. 2010 May;16(3):242-50. doi: 10.1097/MCP.0b013e328337d6de.
When functioning properly, the immune system recognizes inhaled fungi and controls their growth, while avoiding injurious inflammation and allergy. 'Aspergillosis' represents a spectrum of clinical diseases resulting from impaired or excessive immune responses. Invasive aspergillosis is principally disease of severely immunocompromised patients, whereas allergic forms of aspergillosis result from an excessive inflammatory response to hyphae colonizing the sinopulmonary tract. We will review insights gained in host defense against Aspergillus species and the immunopathogenesis of Aspergillus-related diseases as well as important advances made in fungal diagnostics and antifungal therapy.
Important advances have been made in diagnosis of invasive aspergillosis and in antifungal agents. Voriconazole was superior to amphotericin B deoxycholate as primary therapy for invasive aspergillosis. There is significant interest in combination antifungal therapy for invasive aspergillosis. Fungal genomics offers a powerful opportunity to gain knowledge about fungal virulence factors that can be targets for drug development. In addition, new insights have been gained regarding host defense against Aspergillus species that may be exploited therapeutically.
We have gained substantial knowledge regarding how the immune system recognizes inhaled fungi and calibrates the inflammatory response. There has also been substantial progress in tools to diagnose aspergillosis and in antifungal therapeutics. Future progress will likely involve the development of more refined diagnostic tools, new classes of antifungal agents, and greater knowledge of pathogen and host factors that predispose to aspergillosis.
当免疫系统正常运作时,它能够识别吸入的真菌并控制其生长,同时避免产生有害的炎症和过敏反应。“曲霉病”代表了一系列由免疫反应受损或过度引起的临床疾病。侵袭性曲霉病主要发生于严重免疫功能低下的患者,而变态反应性曲霉病则是由于定植于鼻-肺通道的菌丝引起过度炎症反应所致。我们将综述宿主对曲霉菌防御机制的认识以及与曲霉病相关疾病的免疫发病机制方面的进展,以及在真菌诊断和抗真菌治疗方面的重要进展。
在侵袭性曲霉病的诊断和抗真菌药物方面取得了重要进展。伏立康唑作为侵袭性曲霉病的一线治疗药物优于两性霉素 B 去氧胆酸盐。联合抗真菌治疗侵袭性曲霉病的方法引起了广泛关注。真菌基因组学为了解真菌毒力因子提供了一个强有力的机会,这些因子可能成为药物开发的靶点。此外,人们对宿主防御曲霉菌的机制有了新的认识,这些认识可能具有治疗应用价值。
我们已经获得了大量关于免疫系统如何识别吸入的真菌并调节炎症反应的知识。在诊断曲霉病和抗真菌治疗方面也取得了很大的进展。未来的进展可能涉及开发更精确的诊断工具、新型抗真菌药物以及更深入地了解导致曲霉病的病原体和宿主因素。