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 () and Ramnik J. Xavier
Additional contact information
Sanne P. Smeekens: Radboud University Nijmegen Medical Centre
Aylwin Ng: The Broad Institute of Massachusetts Institute of Technology and Harvard University, 7 Cambridge Center
Vinod Kumar: University Medical Centre Groningen
Melissa D. Johnson: Duke University Medical Center
Theo S. Plantinga: Radboud University Nijmegen Medical Centre
Cleo van Diemen: University Medical Centre Groningen
Peer Arts: Radboud University Nijmegen Medical Center
Eugène T. P. Verwiel: Radboud University Nijmegen Medical Center
Mark S. Gresnigt: Radboud University Nijmegen Medical Centre
Karin Fransen: University Medical Centre Groningen
Suzanne van Sommeren: University Medical Centre Groningen
Marije Oosting: Radboud University Nijmegen Medical Centre
Shih-Chin Cheng: Radboud University Nijmegen Medical Centre
Leo A. B. Joosten: Radboud University Nijmegen Medical Centre
Alexander Hoischen: Radboud University Nijmegen Medical Center
Bart-Jan Kullberg: Radboud University Nijmegen Medical Centre
William K. Scott: University of Miami, Miller School of Medicine
John R. Perfect: Duke University Medical Center
Jos W. M. van der Meer: Radboud University Nijmegen Medical Centre
Cisca Wijmenga: University Medical Centre Groningen
Mihai G. Netea: Radboud University Nijmegen Medical Centre
Ramnik J. Xavier: The Broad Institute of Massachusetts Institute of Technology and Harvard University, 7 Cambridge Center

Nature Communications, 2013, vol. 4, issue 1, 1-10

Abstract: Abstract 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.

Date: 2013
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DOI: 10.1038/ncomms2343

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