Department of Experimental Medicine and Biochemical Sciences, University of Perugia Perugia, Italy.
Front Immunol. 2012 Jun 13;3:156. doi: 10.3389/fimmu.2012.00156. eCollection 2012.
Resistance and tolerance are two complementary host defense mechanisms that increase fitness in response to low-virulence fungi. Resistance is meant to reduce pathogen burden during infection through innate and adaptive immune mechanisms, whereas tolerance mitigates the substantial cost of resistance to host fitness through a multitude of anti-inflammatory mechanisms, including immunological tolerance. In experimental fungal infections, both defense mechanisms are activated through the delicate equilibrium between Th1/Th17 cells, which provide antifungal resistance, and regulatory T cells limiting the consequences of the ensuing inflammatory pathology. Indoleamine 2,3-dioxygenase (IDO), a rate-limiting enzyme in the tryptophan catabolism, plays a key role in induction of tolerance against fungi. Both hematopoietic and non-hematopoietic compartments contribute to the resistance/tolerance balance against Aspergillus fumigatus via the involvement of selected innate receptors converging on IDO. Several genetic polymorphisms in pattern recognition receptors influence resistance and tolerance to fungal infections in human hematopoietic transplantation. Thus, tolerance mechanisms may be exploited for novel diagnostics and therapeutics against fungal infections and diseases.
耐药性和耐受性是两种互补的宿主防御机制，可提高对低毒真菌的适应性。耐药性旨在通过先天和适应性免疫机制降低感染期间的病原体负担，而耐受性则通过多种抗炎机制（包括免疫耐受）减轻对宿主适应性的巨大代价。在实验性真菌感染中，通过 Th1/Th17 细胞之间的微妙平衡来激活这两种防御机制，Th1/Th17 细胞提供抗真菌耐药性，而调节性 T 细胞则限制随之而来的炎症病理的后果。吲哚胺 2,3-双加氧酶 (IDO) 是色氨酸分解代谢中的限速酶，在诱导对真菌的耐受性方面起着关键作用。造血和非造血隔室均通过参与 IDO 的选定先天受体，对曲霉菌的耐药性/耐受性平衡做出贡献。模式识别受体中的几种遗传多态性影响人类造血移植中对真菌感染和疾病的耐药性和耐受性。因此，耐受机制可被用于开发针对真菌感染和疾病的新型诊断和治疗方法。
