Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans

被引：148

作者：

Smeekens, Sanne P. ^{[1
,2
]}

Ng, Aylwin ^{[3
,4
,5
]}

Kumar, Vinod ^{[6
]}

Johnson, Melissa D. ^{[7
,8
]}

Plantinga, Theo S. ^{[1
,2
]}

van Diemen, Cleo ^{[6
]}

Arts, Peer ^{[9
]}

Verwiel, Eugene T. P. ^{[9
]}

Gresnigt, Mark S. ^{[1
,2
]}

Fransen, Karin ^{[6
]}

van Sommeren, Suzanne ^{[6
]}

Oosting, Marije ^{[1
,2
]}

Cheng, Shih-Chin ^{[1
,2
]}

Joosten, Leo A. B. ^{[1
,2
]}

Hoischen, Alexander ^{[9
]}

Kullberg, Bart-Jan ^{[1
,2
]}

Scott, William K. ^{[10
,11
]}

Perfect, John R. ^{[7
,8
]}

van der Meer, Jos W. M. ^{[1
,2
]}

Wijmenga, Cisca ^{[6
]}

Netea, Mihai G. ^{[1
,2
]}

Xavier, Ramnik J. ^{[3
,4
,5
]}

机构：

[1] Radboud Univ Nijmegen, Med Ctr, Dept Med 463, NL-6525 GA Nijmegen, Netherlands

[2] Nijmegen Inst Infect Inflammat & Immun N4i 463, NL-6500 HB Nijmegen, Netherlands

[3] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge Ctr 7, Cambridge, MA 02142 USA

[4] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA

[5] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA

[6] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands

[7] Duke Univ, Med Ctr, Durham, NC 27710 USA

[8] Campbell Univ, Sch Pharm, Dept Clin Res, Buies Creek, NC 27506 USA

[9] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet 855, NL-6500 HB Nijmegen, Netherlands

[10] Univ Miami, Miller Sch Med, Dept Human Genet, Dr John T Macdonald Fdn, Miami, FL 33136 USA

[11] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA

来源：

NATURE COMMUNICATIONS | 2013年 / 4卷

基金：

美国国家卫生研究院;

关键词：

BLOOD-STREAM INFECTIONS; EPIDEMIOLOGY; RECOGNITION; EXPRESSION; HOSPITALS; CLASSIFICATION; SUSCEPTIBILITY; ASSOCIATION; TRIGGERS; IMMUNITY;

D O I：

10.1038/ncomms2343

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Candida albicans is the most common human fungal pathogen causing mucosal and systemic infections. However, human antifungal immunity remains poorly defined. Here by integrating transcriptional analysis and functional genomics, we identified Candida-specific host defence mechanisms in humans. Candida induced significant expression of genes from the type I interferon pathway in human peripheral blood mononuclear cells. This unexpectedly prominent role of type I interferon pathway in anti-Candida host defence was supported by additional evidence. Polymorphisms in type I interferon genes modulated Candida-induced cytokine production and were correlated with susceptibility to systemic candidiasis. In in vitro experiments, type I interferons skewed Candida-induced inflammation from a Th17 response towards a Th1 response. Patients with chronic mucocutaneous candidiasis displayed defective expression of genes in the type I interferon pathway. These findings indicate that the type I interferon pathway is a main signature of Candida-induced inflammation and has a crucial role in anti-Candida host defence in humans.

引用

页数：10

共 48 条

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