Dermatophytes activate skin keratinocytes via mitogen-activated protein kinase signaling and induce immune responses.
Dermatophytes activate skin keratinocytes via mitogen-activated protein kinase signaling and induce immune responses.
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DOI：
10.1128/iai.02776-14
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发表时间：
2015-04
影响因子：
3.1
通讯作者：
Naglik JR
中科院分区：
文献类型：
--
作者：
Achterman RR;Moyes DL;Thavaraj S;Smith AR;Blair KM;White TC;Naglik JR
皮肤真菌在免疫活性宿主中引起浅表和皮肤真菌感染，在免疫功能低下宿主中引起侵袭性疾病。然而，调节针对这些真菌的先天免疫应答的宿主机制在很大程度上是未知的。在这里，我们利用市售的表皮组织和原代角质形成细胞来评估（i）嗜热性、嗜土性和嗜动物性皮肤真菌菌株的损伤诱导，以及（ii）代表性皮肤真菌马毛癣菌诱导的角质形成细胞信号传导途径、转录因子和促炎反应。最初，测试了五种皮肤真菌的侵入能力，导致组织损伤，并诱导细胞因子，石膏样小孢子菌诱导最大水平的损伤和细胞因子释放。利用T.结果发现，在马皮肤癣菌中，MAPK通路受到明显影响，磷酸化p38和磷酸化JNK水平升高，磷酸化细胞外信号调节激酶1和2（ERK 1/2）水平降低。值得注意的是，NF-κB和PI 3 K途径基本上不受影响。T.马也显著增加AP-1相关转录因子c-Fos和MAPK调节磷酸酶MKP 1的表达。重要的是，T.马的皮肤真菌能够入侵，引起组织损伤，激活信号和转录因子，并诱导与萌发相关的促炎反应，表明萌发可能对皮肤真菌的毒力和宿主免疫激活很重要。
Dermatophytes cause superficial and cutaneous fungal infections in immunocompetent hosts and invasive disease in immunocompromised hosts. However, the host mechanisms that regulate innate immune responses against these fungi are largely unknown. Here, we utilized commercially available epidermal tissues and primary keratinocytes to assess (i) damage induction by anthropophilic, geophilic, and zoophilic dermatophyte strains and (ii) the keratinocyte signaling pathways, transcription factors, and proinflammatory responses induced by a representative dermatophyte, Trichophyton equinum. Initially, five dermatophyte species were tested for their ability to invade, cause tissue damage, and induce cytokines, with Microsporum gypseum inducing the greatest level of damage and cytokine release. Using T. equinum as a representative dermatophyte, we found that the mitogen-activated protein kinase (MAPK) pathways were predominantly affected, with increased levels of phospho-p38 and phospho-Jun N-terminal protein kinase (JNK) but decreased levels of phospho-extracellular signal-regulated kinases 1 and 2 (ERK1/2). Notably, the NF-κB and PI3K pathways were largely unaffected. T. equinum also significantly increased expression of the AP-1-associated transcription factor, c-Fos, and the MAPK regulatory phosphatase, MKP1. Importantly, the ability of T. equinum to invade, cause tissue damage, activate signaling and transcription factors, and induce proinflammatory responses correlated with germination, indicating that germination may be important for dermatophyte virulence and host immune activation.