Romani Luigina, Zelante Teresa, De Luca Antonella, Fallarino Francesca, Puccetti Paolo
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
J Immunol. 2008 Apr 15;180(8):5157-62. doi: 10.4049/jimmunol.180.8.5157.
Largely viewed as proinflammatory, innate responses combine with adaptive immunity to generate the most effective form of antifungal resistance, and T cells exercise feedback control over diverse effects of inflammation on infection. Some degree of inflammation is required for protection, particularly in mucosal tissues, during the transitional response occurring between the rapid innate and slower adaptive response. However, progressive inflammation worsens disease and ultimately prevents pathogen eradication. IDO, tryptophan catabolites ("kynurenines"), and regulatory T cells help to tame overzealous and exaggerated inflammatory responses. In this context, IL-23 and the Th17 pathway, which down-regulate tryptophan catabolism, may instead favor pathology and serve to accommodate the seemingly paradoxical association of chronic inflammation with fungal persistence. Recent data support a view in which IL-23/IL-17 antagonistic strategies, including the administration of synthetic kynurenines, could represent a new means of harnessing progressive or potentially harmful inflammation.
固有免疫反应在很大程度上被视为促炎反应，它与适应性免疫相结合，产生最有效的抗真菌抵抗形式，并且T细胞对炎症对感染的多种影响进行反馈控制。在快速的固有免疫反应和较慢的适应性免疫反应之间发生的过渡反应期间，一定程度的炎症对于保护是必需的，尤其是在黏膜组织中。然而，进行性炎症会使疾病恶化，并最终阻碍病原体的根除。吲哚胺2,3-双加氧酶（IDO）、色氨酸分解代谢产物（“犬尿氨酸”）和调节性T细胞有助于抑制过度和夸张的炎症反应。在这种情况下，下调色氨酸分解代谢的白细胞介素-23（IL-23）和辅助性T细胞17（Th17）途径可能反而有利于病理过程，并有助于解释慢性炎症与真菌持续存在之间看似矛盾的关联。最近的数据支持这样一种观点，即包括给予合成犬尿氨酸在内的IL-23/IL-17拮抗策略可能代表了一种利用进行性或潜在有害炎症的新方法。
