Wong Sarah Sze Wah, Dellière Sarah, Lepas Mathieu, Aimanianda Vishukumar
Institut Pasteur, Université de Paris, Molecular Mycology Unit, UMR2000, CNRS, Paris, France.
Laboratoire de Parasitologie-Mycologie, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal, Assistance Publique-Hôpitaux de Paris, Paris, France.
Adv Exp Med Biol. 2025;1476:225-250. doi: 10.1007/978-3-031-85340-1_9.
Despite being common inhabitants of human barrier surfaces (skin, oral cavity, gut, lungs, vagina), diseases caused by fungi are rare owing to their surveillance by and sentinel function of human innate immune system. Whereas a compromised or suppressed immunity facilitates the establishment of fungal infections, the consequence of which ranges from superficial infections affecting life quality to life-threatening invasive fungal diseases. Over the last few decades, the number of people at risk for invasive fungal infections has increased due to immunosuppressive medical interventions. Also, there is an alarming increase in incidence of antifungal drug resistance, which demands alternative antifungal strategies. In vivo experimental studies have indicated that immunotherapies could be promising to combat fungal pathogens. Nevertheless, development of an effective clinical immunotherapy requires in-depth knowledge on pathobiology of fungi and the consequent host responses. Here is an overview of the defense mechanisms exerted by the human innate immune system against fungal pathogens, counteracting virulence mechanisms associated with these fungal pathogens and the innate immune system-based antifungal therapeutic strategies developed so far.
尽管真菌是人类屏障表面（皮肤、口腔、肠道、肺部、阴道）的常见寄居菌，但由于人类固有免疫系统对其进行监测并发挥哨兵功能，由真菌引起的疾病却很罕见。而免疫功能受损或受到抑制会促使真菌感染的发生，其后果从影响生活质量的浅表感染到危及生命的侵袭性真菌病不等。在过去几十年中，由于免疫抑制性医疗干预，面临侵袭性真菌感染风险的人数有所增加。此外，抗真菌药物耐药性的发生率惊人地上升，这就需要 alternative antifungal strategies。体内实验研究表明，免疫疗法有望对抗真菌病原体。然而，要开发有效的临床免疫疗法，需要深入了解真菌的病理生物学以及随之而来的宿主反应。以下是人类固有免疫系统针对真菌病原体所发挥的防御机制、对抗与这些真菌病原体相关的毒力机制以及迄今为止基于固有免疫系统开发的抗真菌治疗策略的概述。
