Lack of Toll IL-1R8 exacerbates Th17 cell responses in fungal infection
Lack of Toll IL-1R8 exacerbates Th17 cell responses in fungal infection
复制标题
DOI：
10.4049/jimmunol.180.6.4022
复制
发表时间：
2008-03-15
影响因子：
4.4
通讯作者：
Romani, Luigina
中科院分区：
文献类型：
--
作者：
Bozza, Silvia;Zelante, Teresa;Romani, Luigina
TLRs在真菌感染的炎症反应中起作用。虽然炎症是对真菌的保护性反应的重要组成部分，但它的失调可能会显著加重真菌疾病。在这项研究中，我们验证了IL-1R家族成员Toll IL-1R8(T1R8)/单个Ig IL-1相关受体作为TLR/IL-1R信号负调节因子影响真菌感染TLR反应的假设。对Tir8(-/-)转基因小鼠的炎症反应和适应性Th细胞对白色念珠菌和烟曲霉菌的反应进行了评估。Tir8(-/-)小鼠的炎症病理和感染易感性更高，与Th17途径的激活有因果关系。IL-1R信号转导参与了IL-6和转化生长因子-β对Th17细胞的激活，在IL-1RI(-/-)小鼠可见局限性的炎症病理改变和Th17细胞的相对缺失。这些数据表明，T1R8是宿主抵抗真菌感染所必需的，它的功能是负向调节IL-1依赖的炎症性Th17反应的激活。T1R8可能有助于微调感染中保护性免疫和免疫病理之间的平衡。
TLRs contribute to the inflammatory response in fungal infections. Although inflammation is an essential component of the protective response to fungi, its dysregulation may significantly worsen fungal diseases. In this study, we tested the hypothesis that Toll IL-1R8 (T1R8)/single Ig IL-1-related receptor, a member of the IL-1R family acting as a negative regulator of TLR/IL-1R signaling, affects TLR responses in fungal infections. Genetically engineered Tir8(-/-) mice were assessed for inflammatory and adaptive Th cell responses to Candida albicans and Aspergillus fumigatus. Inflammatory pathology and susceptibility to infection were higher in Tir8(-/-) mice and were causally linked to the activation of the Th17 pathway. IL-1R signaling was involved in Th17 cell activation by IL-6 and TGF-beta in that limited inflammatory pathology and relative absence of Th17 cell activation were observed in IL-1RI(-/-) mice. These data demonstrate that T1R8 is required for host resistance to fungal infections and that it functions to negatively regulate IL-1-dependent activation of inflammatory Th17 responses. T1R8 may contribute toward fine-tuning the balance between protective immunity and immunopathology in infection.