A biphasic innate immune MAPK response discriminates between the yeast and hyphal forms of Candida albicans in epithelial cells.
A biphasic innate immune MAPK response discriminates between the yeast and hyphal forms of Candida albicans in epithelial cells.
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DOI：
10.1016/j.chom.2010.08.002
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发表时间：
2010-09-16
影响因子：
30.3
通讯作者：
Naglik JR
中科院分区：
文献类型：
--
作者：
Moyes DL;Runglall M;Murciano C;Shen C;Nayar D;Thavaraj S;Kohli A;Islam A;Mora-Montes H;Challacombe SJ;Naglik JR
区分条件致病菌的寄生状态和致病状态对于宿主的粘膜防御和体内平衡是至关重要的。机会性人类真菌病原体白色念珠菌也是正常口腔植物群的组成部分，并且以酵母或菌丝的形式生长。我们证明口腔上皮细胞通过NF-κB和双相MAPK应答来协调对白色念珠菌的先天应答。NF-κB和第一MAPK相的激活，构成c-Jun激活，与形态学无关，并且是由于真菌细胞壁识别。第二MAPK阶段的激活，构成MKP 1和c-Fos激活，是依赖于菌丝形成和真菌的负担，并与促炎反应。这种双相反应可能允许上皮组织在低真菌负荷下保持静止，而在负荷增加时对损伤诱导菌丝做出特异性和强烈的反应。MAPK/MKP 1/c-Fos的激活可能代表了一种“危险反应”途径，这对于识别和响应肠道微生物的致病开关至关重要。NF-κB和MAPK控制上皮细胞对白色念珠菌的效应反应。c-Jun的激活不依赖于形态学，由于真菌细胞壁的识别，MAPK/MKP-1/c-Fos通路的激活依赖于真菌菌丝和负担。体内白色念珠菌粘膜定植
Discriminating between commensal and pathogenic states of opportunistic pathogens is critical for host mucosal defense and homeostasis. The opportunistic human fungal pathogen Candida albicans is also a constituent of the normal oral flora and grows either as yeasts or hyphae. We demonstrate that oral epithelial cells orchestrate an innate response to C. albicans via NF-κB and a biphasic MAPK response. Activation of NF-κB and the first MAPK phase, constituting c-Jun activation, is independent of morphology and due to fungal cell wall recognition. Activation of the second MAPK phase, constituting MKP1 and c-Fos activation, is dependent upon hypha formation and fungal burdens and correlates with proinflammatory responses. Such biphasic response may allow epithelial tissues to remain quiescent under low fungal burdens while responding specifically and strongly to damage-inducing hyphae when burdens increase. MAPK/MKP1/c-Fos activation may represent a “danger response” pathway that is critical for identifying and responding to the pathogenic switch of commensal microbes. ► NF-κB and MAPK control epithelial effector responses against Candida albicans ► c-Jun activation is independent of morphology and due to fungal cell wall recognition ► MAPK/MKP-1/c-Fos pathway activation is dependent on fungal hyphae and burdens ► MAPK discriminatory response may dictate C. albicans mucosal colonization in vivo
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影响因子：
64.5
作者：
Lo, HJ;Kohler, JR;Fink, GR
通讯作者：
Fink, GR
影响因子：
15.9
作者：
Dillon, S;Agrawal, S;Pulendran, B
通讯作者：
Pulendran, B
影响因子：
3.6
作者：
Murad, AMA;d'Enfert, C;Brown, AJP
通讯作者：
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影响因子：
2.6
作者：
GOW, NAR;GOODAY, GW;GULL, K
通讯作者：
GULL, K
DOI：
10.1016/j.niox.2008.12.004
发表时间：
2009-05
期刊：
Nitric oxide : biology and chemistry
影响因子：
--
作者：
Chambellan A;Leahy R;Xu W;Cruickshank PJ;Janocha A;Szabo K;Cannady SB;Comhair SA;Erzurum SC
通讯作者：
Erzurum SC