Activation of MAPK/c-Fos induced responses in oral epithelial cells is specific to Candida albicans and Candida dubliniensis hyphae.

Activation of MAPK/c-Fos induced responses in oral epithelial cells is specific to Candida albicans and Candida dubliniensis hyphae.
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口腔上皮细胞中MAPK/c-FOS诱导反应的激活特异于白色念珠菌和都柏林菌丝菌丝。

DOI:
10.1007/s00430-011-0209-y
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发表时间:
2012-02
影响因子:
5.4
通讯作者:
Naglik JR
Naglik JR
中科院分区:
医学2区
文献类型:
--
作者:
Moyes DL;Murciano C;Runglall M;Kohli A;Islam A;Naglik JR

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口腔上皮细胞通过NF-κB和双相丝裂原活化蛋白激酶(MAPK)信号应答检测人类致病真菌白色念珠菌。然而,C.白念珠菌酵母和菌丝形式仅由MAPK途径介导,其构成MAPK磷酸酶MKP 1和c-Fos转录因子的活化,并靶向菌丝形式。考虑到C.白念珠菌不是唯一能够引起粘膜感染的念珠菌属,我们试图确定这种MAPK/MKP 1/c-Fos介导的反应机制是否被其他致病念珠菌属激活,包括念珠菌。dubliniensis、C. tropicalis、热带假丝酵母C. parapsilosis,C.光萼假丝酵母C. krusei。虽然所有念珠菌都激活了NF-κB信号通路,但只有C.白色念珠菌和C. dubliniensis能够诱导MKP 1和c-Fos活化,这与菌丝形成直接相关。然而,只有C.白念珠菌可强烈诱导细胞因子(G-CSF、GM-CSF、IL-6和IL-1α)的产生和细胞损伤。都柏林假丝酵母(Candida dubliniensis)、C.和C.近平滑病也能够诱导IL-1α,这与轻度细胞损伤相关,并依赖于真菌负荷。我们的数据表明,MAPK/MKP 1/c-Fos通路在口腔上皮细胞中的激活是C. dubliniensis和C.白色念珠菌菌丝
Oral epithelial cells detect the human pathogenic fungus Candida albicans via NF-κB and a bi-phasic mitogen-activated protein kinase (MAPK) signaling response. However, discrimination between C. albicans yeast and hyphal forms is mediated only by the MAPK pathway, which constitutes activation of the MAPK phosphatase MKP1 and the c-Fos transcription factor and is targeted against the hyphal form. Given that C. albicans is not the only Candida species capable of filamentation or causing mucosal infections, we sought to determine whether this MAPK/MKP1/c-Fos mediated response mechanism was activated by other pathogenic Candida species, including C. dubliniensis, C. tropicalis, C. parapsilosis, C. glabrata and C. krusei. Although all Candida species activated the NF-κB signaling pathway, only C. albicans and C. dubliniensis were capable of inducing MKP1 and c-Fos activation, which directly correlated with hypha formation. However, only C. albicans strongly induced cytokine production (G-CSF, GM-CSF, IL-6 and IL-1α) and cell damage. Candida dubliniensis, C. tropicalis and C. parapsilosis were also capable of inducing IL-1α and this correlated with mild cell damage and was dependent upon fungal burdens. Our data demonstrate that activation of the MAPK/MKP1/c-Fos pathway in oral epithelial cells is specific to C. dubliniensis and C. albicans hyphae.
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