The contribution of the Toll-like/IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens in vivo
The contribution of the Toll-like/IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens in vivo
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DOI：
10.4049/jimmunol.172.5.3059
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发表时间：
2004-03-01
影响因子：
4.4
通讯作者：
Romani, L
中科院分区：
文献类型：
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作者：
Bellocchio, S;Montagnoli, C;Romani, L
体外研究表明，Toll样受体（TLR）信号在响应真菌病原体白色念珠菌和烟曲霉中的重要性。然而，在体内真菌形态发生和TLR信号之间的复杂相互作用的功能性后果仍然在很大程度上不确定。在这项研究中，我们评估IL-1 R/TLR/髓样分化初级反应基因88（MyD 88）依赖的信号通路对先天性和适应性Th免疫的影响。白色念珠菌和A.烟曲霉菌发现1）MyD 88依赖性途径是对两种真菌的抗性所必需的; 2）MyD 88衔接子的参与可能通过IL-1 R/TLR超家族的不同成员（包括IL-1 R、TLR 2、TLR 4和TLR 9）的信号传导而发生，其中个体受体的比例作用根据真菌物种、真菌形态型和感染途径而变化; 3）单个TLR和IL-1 R激活嗜中性粒细胞上的特异性抗真菌效应子功能，这与感染易感性相关;以及4）树突状细胞上的MyD 88依赖性信号传导对于引发抗真菌Th 1应答至关重要。因此，研究发现，先天性和适应性免疫C。白色念珠菌和A.烟曲霉的抗性需要IL-1 R/TLR超家族的不同成员通过MyD 88起作用的协调作用，使得TLR操纵适合于诱导宿主对真菌的抗性。
In vitro studies have indicated the importance of Toll-like receptor (TLR) signaling in response to the fungal pathogens Candida albicans and Aspergillus fumigatus. However, the functional consequences of the complex interplay between fungal morphogenesis and TLR signaling in vivo remain largely undefined. In this study we evaluate the impact of the IL-1R/TLR/myeloid differentiation primary response gene 88 (MyD88)-dependent signaling pathway on the innate and adaptive Th immunities to C. albicans and A. fumigatus in vivo. It was found that 1) the MyD88-dependent pathway is required for resistance to both fungi; 2) the involvement of the MyD88 adapter may occur through signaling by distinct members of the IL-1R/TLR superfamily, including IL-1R, TLR2, TLR4, and TLR9, with the proportional role of the individual receptors varying depending on fungal species, fungal morphotypes, and route of infection; 3) individual TLRs and IL-1R activate specialized antifungal effector functions on neutrophils, which correlates with susceptibility to infection; and 4) MyD88-dependent signaling on dendritic cells is crucial for priming antifungal Th1 responses. Thus, the finding that the innate and adaptive immunities to C. albicans and A. fumigatus require the coordinated action of distinct members of the IL-1R/TLR superfamily acting through MyD88 makes TLR manipulation amenable to the induction of host resistance to fungi.