IL-17 Receptor Signaling in Oral Epithelial Cells Is Critical for Protection against Oropharyngeal Candidiasis.
IL-17 Receptor Signaling in Oral Epithelial Cells Is Critical for Protection against Oropharyngeal Candidiasis.
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DOI：
10.1016/j.chom.2016.10.001
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发表时间：
2016-11-09
影响因子：
30.3
通讯作者：
Gaffen SL
中科院分区：
文献类型：
--
作者：
Conti HR;Bruno VM;Childs EE;Daugherty S;Hunter JP;Mengesha BG;Saevig DL;Hendricks MR;Coleman BM;Brane L;Solis N;Cruz JA;Verma AH;Garg AV;Hise AG;Richardson JP;Naglik JR;Filler SG;Kolls JK;Sinha S;Gaffen SL
在小鼠和人类中，通过IL-17受体（IL-17R）发出信号是预防口咽念珠菌病（OPC）所必需的。然而，介导保护的il -17应答细胞类型尚不清楚。使用放射嵌合体，我们能够排除造血室中IL-17RA的需求。我们在白色念珠菌感染的人口腔上皮细胞（OECs）和OPC小鼠的舌组织中发现了il -17控制的基因表达的显著一致性。为了探究IL-17R在oec中的作用，我们在口腔和食管浅表上皮细胞中产生条件缺失IL-17RA的小鼠（Il17raΔK13）。在口腔念珠菌感染后，Il17raΔK13小鼠表现出真菌负荷和体重减轻，与Il17ra - / -小鼠没有区别。Il17raΔK13小鼠的敏感性与抗菌肽β-防御素3 （BD3, Defb3）的表达相关。与此一致，Defb3−/−小鼠对OPC易感。因此，oec主要通过调节bd3的表达来控制il - 17r依赖性的OPC应答。IL-17受体信号是预防小鼠和人类口咽念珠菌病（“鹅口疮”）所必需的。Conti等人在小鼠实验中证明，口腔浅表上皮细胞（OECs）中依赖il - 17r的抗真菌反应对保护至关重要。此外，oec主要通过产生抗菌肽β-防御素3来控制il - 17r依赖性反应。
Signaling through the IL-17 receptor (IL-17R) is required to prevent oropharyngeal candidiasis (OPC) in mice and humans. However, the IL-17-responsive cell type(s) that mediate protection are unknown. Using radiation chimeras we were able to rule out a requirement for IL-17RA in the hematopoietic compartment. We saw remarkable concordance of IL-17-controlled gene expression in C. albicans-infected human oral epithelial cells (OECs) and in tongue tissue from mice with OPC. To interrogate the role of the IL-17R in OECs, we generated mice with conditional deletion of IL-17RA in superficial oral and esophageal epithelial cells (Il17raΔK13). Following oral Candida infection, Il17raΔK13 mice exhibited fungal loads and weight loss indistinguishable from Il17ra−/− mice. Susceptibility in Il17raΔK13 mice correlated with expression of the antimicrobial peptide β-defensin 3 (BD3, Defb3). Consistently, Defb3−/− mice were susceptible to OPC. Thus, OECs dominantly control IL-17R-dependent responses to OPC through regulation of BD3expression. IL-17 receptor signaling is required to prevent oropharyngeal candidiasis (“oral thrush”) in both mice and humans. Conti et al. demonstrate in mice that IL-17R-dependent anti-fungal responses in superficial oral epithelial cells (OECs) are critical for protection. Moreover, OECs dominantly control IL-17R-dependent responses through production of the antimicrobial peptide β-defensin 3.
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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
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：
4.9
作者：
Kamai, Y;Kubota, M;Filler, SG
通讯作者：
Filler, SG
影响因子：
4.9
作者：
Edgerton, M;Koshlukova, SE;Bruenn, JA
通讯作者：
Bruenn, JA
中性粒细胞在IL-17依赖性粘膜念珠菌病中的作用。
DOI：
10.4049/jimmunol.1302265
发表时间：
2014-02-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Huppler AR;Conti HR;Hernández-Santos N;Darville T;Biswas PS;Gaffen SL
通讯作者：
Gaffen SL