The RIG-I-like helicase receptor MDA5 (IFIH1) is involved in the host defense against Candida infections.
The RIG-I-like helicase receptor MDA5 (IFIH1) is involved in the host defense against Candida infections.
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RIG-I 样解旋酶受体 MDA5 (IFIH1) 参与宿主针对念珠菌感染的防御
DOI：
10.1007/s10096-014-2309-2
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发表时间：
2015-05
影响因子：
4.5
通讯作者：
Netea, M. G.
中科院分区：
文献类型：
--
作者：
Jaeger, M.;van der Lee, R.;Cheng, S-C.;Johnson, M. D.;Kumar, V.;Ng, A.;Plantinga, T. S.;Smeekens, S. P.;Oosting, M.;Wang, X.;Barchet, W.;Fitzgerald, K.;Joosten, L. A. B.;Perfect, J. R.;Wijmenga, C.;van de Veerdonk, F. L.;Huynen, M. A.;Xavier, R. J.;Kullberg, B. J.;Netea, M. G.
宿主对念珠菌属物种的防御的诱导是通过模式识别受体识别真菌并激活产生清除感染所必需的炎症介质的下游途径来启动的。在本研究中，我们基于基因敲除小鼠和人类的转录组分析、遗传学和免疫学研究提供了补充证据，表明胞质 RIG-I 样受体 MDA5 (IFIHI) 在宿主针对白色念珠菌的防御中发挥着重要作用。首先，巨噬细胞中的IFIH1表达是由侵入性白色念珠菌菌丝特异性诱导的，患有慢性皮肤粘膜念珠菌病（CMC）的患者表达的MDA5水平低于健康对照。其次，IFIH1 基因中的错义变异（rs1990760 和 rs3747517）与全身性念珠菌感染的易感性之间存在密切关联。第三，来自 Mda5 敲除小鼠和具有不同 IFIH1 基因型的人类 PBMC 的细胞对白色念珠菌表现出改变的细胞因子反应。这些数据强烈表明 MDA5 参与对念珠菌感染的免疫反应。作为病毒 RNA 的受体，MDA5 受体迄今为止一直与抗病毒宿主防御有关，但这些新研究在抗真菌免疫方面也显示出意想不到的效果。未来的研究有必要探索 MDA5 作为免疫治疗策略新靶点的潜力。
The induction of host defense against Candida species is initiated by recognition of the fungi by pattern recognition receptors and activation of downstream pathways that produce inflammatory mediators essential for infection clearance. In the present study, we present complementary evidence based on transcriptome analysis, genetics, and immunological studies in knockout mice and humans, that the cytosolic RIG-I-like receptor MDA5 (IFIHI) has an important role in the host defense against C. albicans. Firstly, IFIH1 expression in macrophages is specifically induced by invasive C. albicans hyphae, and patients suffering from chronic mucocutaneous candidiasis (CMC) express lower levels of MDA5 than healthy controls. Secondly, there is a strong association between missense variants in the IFIH1 gene (rs1990760 and rs3747517) and susceptibility to systemic Candida infections. Thirdly, cells from Mda5 knockout mice and human PBMCs with different IFIH1 genotypes display an altered cytokine response to C. albicans. These data strongly suggest that MDA5 is involved in immune responses to Candida infection. As a receptor for viral RNA, MDA5 receptor until now has been linked to antiviral host defense, but these novel studies show unexpected effects in antifungal immunity as well. Future studies are warranted to explore the potential of MDA5 as novel target for immunotherapeutic strategies.
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影响因子：
11.8
作者：
Babula, O;Lazdane, G;Witkin, SS
通讯作者：
Witkin, SS
TLR1/TLR2异二聚体在识别伯氏螺旋体中起着重要作用。
影响因子：
3.7
作者：
Oosting M;Ter Hofstede H;Sturm P;Adema GJ;Kullberg BJ;van der Meer JW;Netea MG;Joosten LA
通讯作者：
Joosten LA
影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
影响因子：
3.2
作者：
LEHRER, RI;CLINE, MJ
通讯作者：
CLINE, MJ
影响因子：
6.4
作者：
Plantinga, Theo S.;Johnson, Melissa D.;Netea, Mihai G.
通讯作者：
Netea, Mihai G.