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

Publication ,  Journal Article
Smeekens, SP; Ng, A; Kumar, V; Johnson, MD; Plantinga, TS; van Diemen, C; Arts, P; Verwiel, ETP; Gresnigt, MS; Fransen, K; van Sommeren, S ...
Published in: Nat Commun
2013

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.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

2013

Volume

4

Start / End Page

1342

Location

England

Related Subject Headings

  • Transcription, Genetic
  • Th17 Cells
  • Th1 Cells
  • Signal Transduction
  • STAT1 Transcription Factor
  • Polymorphism, Single Nucleotide
  • Mutation
  • Interferon Type I
  • Humans
  • Host-Pathogen Interactions
 

Citation

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ICMJE
MLA
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Smeekens, S. P., Ng, A., Kumar, V., Johnson, M. D., Plantinga, T. S., van Diemen, C., … Xavier, R. J. (2013). Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans. Nat Commun, 4, 1342. https://doi.org/10.1038/ncomms2343
Smeekens, Sanne P., Aylwin Ng, Vinod Kumar, Melissa D. Johnson, Theo S. Plantinga, Cleo van Diemen, Peer Arts, et al. “Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans.Nat Commun 4 (2013): 1342. https://doi.org/10.1038/ncomms2343.
Smeekens SP, Ng A, Kumar V, Johnson MD, Plantinga TS, van Diemen C, et al. Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans. Nat Commun. 2013;4:1342.
Smeekens, Sanne P., et al. “Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans.Nat Commun, vol. 4, 2013, p. 1342. Pubmed, doi:10.1038/ncomms2343.
Smeekens SP, Ng A, Kumar V, Johnson MD, Plantinga TS, van Diemen C, Arts P, Verwiel ETP, Gresnigt MS, Fransen K, van Sommeren S, Oosting M, Cheng S-C, Joosten LAB, Hoischen A, Kullberg B-J, Scott WK, Perfect JR, van der Meer JWM, Wijmenga C, Netea MG, Xavier RJ. Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans. Nat Commun. 2013;4:1342.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

2013

Volume

4

Start / End Page

1342

Location

England

Related Subject Headings

  • Transcription, Genetic
  • Th17 Cells
  • Th1 Cells
  • Signal Transduction
  • STAT1 Transcription Factor
  • Polymorphism, Single Nucleotide
  • Mutation
  • Interferon Type I
  • Humans
  • Host-Pathogen Interactions