IL-36 and IL-1/IL-17 Drive Immunity to Oral Candidiasis via Parallel Mechanisms.
IL-36 and IL-1/IL-17 Drive Immunity to Oral Candidiasis via Parallel Mechanisms.
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DOI：
10.4049/jimmunol.1800515
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发表时间：
2018-07-15
期刊：
影响因子：
--
通讯作者：
Moyes DL
中科院分区：
文献类型：
--
作者：
Verma AH;Zafar H;Ponde NO;Hepworth OW;Sihra D;Aggor FEY;Ainscough JS;Ho J;Richardson JP;Coleman BM;Hube B;Stacey M;McGeachy MJ;Naglik JR;Gaffen SL;Moyes DL
通过诱导炎症来防止微生物感染是白细胞介素-1超家族的关键功能，包括经典的IL-1和新的IL-36细胞因子家族。白色念珠菌是一种常见的引起人类粘膜感染的真菌病原体。虽然在宿主对C.虽然对白色念珠菌的描述很好，但驱动这些反应的关键因素仍然定义不清。最近的工作已经确定了IL-1在诱导先天性17型免疫应答以清除C。白色念珠菌感染尽管如此，缺乏IL-1信号传导并不会导致免疫力的完全丧失，这表明还有其他因素参与介导对这种真菌的保护。在这里，我们确定IL-36细胞因子作为一个新的球员在这些反应。我们证明了C.口腔粘膜的白色念珠菌感染诱导IL-36的产生。与IL-1α/β一样，上皮细胞IL-36的诱导依赖于菌丝相关肽毒素--白细胞介素。上皮细胞IL-36基因表达需要p38-MAPK/c-Fos、NF-κB和PI 3 K信号传导，并受MAPK磷酸酶MKP 1调节。IL-36 R −/−小鼠的口腔念珠菌病显示真菌负荷增加和IL-23基因表达减少，表明IL-36和IL-23在对这种真菌的先天保护性反应中发挥关键作用。引人注目的是，我们观察到对IL-17或IL-17依赖性基因的基因表达没有影响，表明这种保护作用是通过IL-1驱动的免疫的替代途径发生的。因此，IL-1和IL-36代表了平行的上皮细胞驱动的保护性途径，在免疫口服C。白色念珠菌感染
Protection against microbial infection by the induction of inflammation is a key function of the interleukin-1 superfamily, including both classical IL-1 and the new IL-36 cytokine families. Candida albicans is a frequent human fungal pathogen causing mucosal infections. Although the initiators and effectors important in protective host responses to C. albicans are well described, the key players in driving these responses remain poorly defined. Recent work has identified a central role played by IL-1 in inducing innate type 17 immune responses to clear C. albicans infections. Despite this, lack of IL-1 signaling does not result in complete loss of immunity, indicating that there are other factors involved in mediating protection to this fungus. Here, we identify IL-36 cytokines as a new player in these responses. We show that C. albicans infection of the oral mucosa induces the production of IL-36. In common with IL-1α/β, induction of epithelial IL-36 depends on the hypha-associated peptide toxin, Candidalysin. Epithelial IL-36 gene expression requires p38-MAPK/c-Fos, NF-κB and PI3K signaling, and is regulated by the MAPK phosphatase MKP1. Oral candidiasis in IL-36R−/− mice shows increased fungal burdens and reduced IL-23 gene expression, indicating a key role played by IL-36 and IL-23 in innate protective responses to this fungus. Strikingly, we observed no impact on gene expression of IL-17 or IL-17-dependent genes, indicating that this protection occurs via an alternative pathway to IL-1-driven immunity. Thus, IL-1 and IL-36 represent parallel epithelial cell-driven protective pathways in immunity to oral C. albicans infection.
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影响因子：
4.4
作者：
Baer, Eva;Gadiator, Andre;LeibundGut-Landmann, Salome
通讯作者：
LeibundGut-Landmann, Salome
DOI：
10.4049/jimmunol.1301481
发表时间：
2014-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Foster AM;Baliwag J;Chen CS;Guzman AM;Stoll SW;Gudjonsson JE;Ward NL;Johnston A
通讯作者：
Johnston A
DOI：
10.4049/jimmunol.1003162
发表时间：
2011-02-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Johnston A;Xing X;Guzman AM;Riblett M;Loyd CM;Ward NL;Wohn C;Prens EP;Wang F;Maier LE;Kang S;Voorhees JJ;Elder JT;Gudjonsson JE
通讯作者：
Gudjonsson JE
影响因子：
3.1
作者：
Ferreira, Maria Carolina;Whibley, Natasha;Gaffen, Sarah L.
通讯作者：
Gaffen, Sarah L.
影响因子：
6.4
作者：
Ahsan, Fadhil;Moura-Alves, Pedro;Maertzdorf, Jeroen
通讯作者：
Maertzdorf, Jeroen