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| Status |
Public on Dec 01, 2012 |
| Title |
Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Candida albicans is the most common human fungal pathogen causing mucosal and systemic infections. However, human antifungal immunity remains poorly defined. By integrating transcriptional analysis and functional genomics we identified Candida-specific host defense mechanisms in humans. Candida induced significant (p<10-35) 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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| Overall design |
3 healthy controls and 2 CMC patients
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| Contributor(s) |
Smeekens SP, Ng A, Kumar V, Johnson MD, Plantinga TS, van Diemen C, Arts P, Verwiel ET, Gresnigt MS, Fransen K, van Sommeren S, Oosting M, Cheng S, Joosten LA, Hoischen A, Kullberg B, Scott WK, Perfect JR, van der Meer JW, Wijmenga C, Netea MG, Xavier RJ |
| Citation(s) |
23299892 |
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| Submission date |
Nov 29, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Eugene Thomas Pieter Verwiel |
| E-mail(s) |
e.verwiel@gen.umcn.nl
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| Organization name |
Radboud University Medical Centre
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| Department |
Human Genetics
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| Street address |
Geert Grooteplein zuid 10
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| City |
Nijmegen |
| State/province |
Gelderland |
| ZIP/Postal code |
6525 GA |
| Country |
Netherlands |
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| Platforms (1) |
| GPL16288 |
AB 5500xl Genetic Analyzer (Homo sapiens) |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA182377 |
| SRA |
SRP017349 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE42630_RAW.tar |
6.8 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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