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

Sanne P Smeekens | Aylwin Ng | Vinod Kumar | Melissa D Johnson | Theo S Plantinga | Cleo van Diemen | Peer Arts | Eugène T P Verwiel | Mark S Gresnigt | Karin Fransen | Suzanne van Sommeren | Marije Oosting | Shih-Chin Cheng | Leo A B Joosten | Alexander Hoischen | Bart-Jan Kullberg | William K Scott | John R Perfect | Jos W M van der Meer | Cisca Wijmenga | Mihai G Netea | Ramnik J Xavier
Nature communications | 2013

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.

Pubmed ID: 23299892

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Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: AI062773
  • Agency: NIDDK NIH HHS, United States
    Id: DK043351
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK043351
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK064869
  • Agency: NIDDK NIH HHS, United States
    Id: DK83756
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI062773
  • Agency: European Research Council, International
    Id: 310372
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK083756

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PLINK (tool)

RRID:SCR_001757

Open source whole genome association analysis toolset, designed to perform range of basic, large scale analyses in computationally efficient manner. Used for analysis of genotype/phenotype data. Through integration with gPLINK and Haploview, there is some support for subsequent visualization, annotation and storage of results. PLINK 1.9 is improved and second generation of the software.

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R Project for Statistical Computing (tool)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

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