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; Eugéne 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

doi:10.1038/ncomms2343

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

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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, Eugéne T.P Verwiel, Mark S Gresnigt, Karin Fransen, …

Nature communications, Vol.4(1), pp.1342-1342

2013

DOI: https://doi.org/10.1038/ncomms2343

PMCID: PMC3625375

PMID: 23299892

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 defense mechanisms in humans. Candida induced significant expression of genes from the type I interferon (IFN) pathway in human peripheral blood mononuclear cells. This unexpectedly prominent role of type I IFN pathway in anti- Candida host defense was supported by additional evidence. Polymorphisms in type I IFN genes modulated Candida -induced cytokine production and were correlated with susceptibility to systemic candidiasis. In in-vitro experiments, type I IFNs skewed Candida -induced inflammation from a Th17-response toward a Th1-response. Patients with chronic mucocutaneaous candidiasis displayed defective expression of genes in the type I IFN pathway. These findings indicate that the type I IFN pathway is a main signature of Candida -induced inflammation and plays a crucial role in anti- Candida host defense in humans.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.148 Medical Mycology; 1.148.94 Candida Albicans
Web Of Science research areas: Immunology
ESI research areas: Immunology

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Title: Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans
Creators: Sanne P Smeekens - Department of Medicine , Radboud University Nijmegen Medical Centre, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands
Aylwin Ng - The Broad Institute of Massachusetts Institute of Technology and Harvard University, 7 Cambridge Center, Cambridge MA 02142, USA
Vinod Kumar - Department of Genetics, University Medical Centre Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands
Melissa D Johnson - Duke University Medical Center, Duke Box 102359, Durham NC 27710 NC, USA
Theo S Plantinga - Department of Medicine , Radboud University Nijmegen Medical Centre, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands
Cleo van Diemen - Department of Genetics, University Medical Centre Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands
Peer Arts - Department of Human Genetics , Radboud University Nijmegen Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands
Eugéne T.P Verwiel - Department of Human Genetics , Radboud University Nijmegen Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands
Mark S Gresnigt - Department of Medicine , Radboud University Nijmegen Medical Centre, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands
Karin Fransen - Department of Genetics, University Medical Centre Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands
Suzanne van Sommeren - Department of Genetics, University Medical Centre Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands
Marije Oosting - Department of Medicine , Radboud University Nijmegen Medical Centre, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands
Shih-Chin Cheng - Department of Medicine , Radboud University Nijmegen Medical Centre, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands
Leo A.B Joosten - Department of Medicine , Radboud University Nijmegen Medical Centre, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands
Alexander Hoischen - Department of Human Genetics , Radboud University Nijmegen Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands
Bart-Jan Kullberg - Department of Medicine , Radboud University Nijmegen Medical Centre, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands
William K Scott - Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, 1501 NW 10th Avenue Miami FL 33136, USA
John R Perfect - Duke University Medical Center, Duke Box 102359, Durham NC 27710 NC, USA
Jos W.M van der Meer - Department of Medicine , Radboud University Nijmegen Medical Centre, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands
Cisca Wijmenga - Department of Genetics, University Medical Centre Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands
Mihai G Netea - Department of Medicine , Radboud University Nijmegen Medical Centre, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands
Ramnik J Xavier - The Broad Institute of Massachusetts Institute of Technology and Harvard University, 7 Cambridge Center, Cambridge MA 02142, USA
Publication Details: Nature communications, Vol.4(1), pp.1342-1342
Academic Unit: Miller School of Medicine; UMMG Dept of Human Genetics - Clinical and Translational Genetics; UMMG Dept of Human Genetics (Dr. John T. Macdonald Foundation)
Language: English
Resource Type: Journal article
PMID: 23299892
PMCID: PMC3625375
Record Identifier: 991031577869102976