Document Detail


Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans.
MedLine Citation:
PMID:  23299892     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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.
Authors:
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
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Nature communications     Volume:  4     ISSN:  2041-1723     ISO Abbreviation:  Nat Commun     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-09     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101528555     Medline TA:  Nat Commun     Country:  England    
Other Details:
Languages:  eng     Pagination:  1342     Citation Subset:  IM    
Affiliation:
1] Department of Medicine (463), Radboud University Nijmegen Medical Centre, Geert Grooteplein Zuid 8, 6525GA Nijmegen, The Netherlands [2] Nijmegen Institute for Infection, Inflammation, and Immunity (N4i) (463), PO Box 9101, 6500 HB Nijmegen, The Netherlands [3].
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