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

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. Candi...

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Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625375/
https://www.ncbi.nlm.nih.gov/pubmed/23299892
http://dx.doi.org/10.1038/ncomms2343
Descripción
Sumario: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.