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

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Title: Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans
Author: Smeekens, Sanne P.; Ng, Aylwin; Kumar, Vinod; Johnson, Melissa D.; Plantinga, Theo S.; van Diemen, Cleo; Arts, Peer; Verwiel, Eugéne T.P.; Gresnigt, Mark S.; Fransen, Karin; van Sommeren, Suzanne; Oosting, Marije; Cheng, Shih-Chin; Joosten, Leo A.B.; Hoischen, Alexander; Kullberg, Bart-Jan; Scott, William K.; Perfect, John R.; van der Meer, Jos W.M.; Wijmenga, Cisca; Netea, Mihai G.; Xavier, Ramnik J.

Note: Order does not necessarily reflect citation order of authors.

Citation: Smeekens, S. P., A. Ng, V. Kumar, M. D. Johnson, T. S. Plantinga, C. van Diemen, P. Arts, et al. 2013. “Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans.” Nature communications 4 (1): 1342. doi:10.1038/ncomms2343. http://dx.doi.org/10.1038/ncomms2343.
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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.
Published Version: doi:10.1038/ncomms2343
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625375/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11717637
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