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

Sanne P. Smeekens; Aylwin Ng; Vinod  Kumar; Melissa D. Johnson; Theo S. Plantinga; Cleo van Diemen; Peer Arts; Eugene 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

doi:10.1038/ncomms2343

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

Sanne P. Smeekens, Aylwin Ng, Vinod Kumar, Melissa D. Johnson, Theo S. Plantinga, Cleo van Diemen, Peer Arts, Eugene 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 WijmengaMihai G. Netea^*, Ramnik J. Xavier

^*Corresponding author for this work

Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)

Research output: Contribution to journal › Article › Academic › peer-review

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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 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.

Original language	English
Article number	1342
Number of pages	10
Journal	Nature Communications
Volume	4
DOIs	https://doi.org/10.1038/ncomms2343
Publication status	Published - Jan-2013

Keywords

BLOOD-STREAM INFECTIONS
LISTERIA-MONOCYTOGENES
GENE-EXPRESSION
UNITED-STATES
RNA-SEQ
EPIDEMIOLOGY
RECOGNITION
MACROPHAGES
HOSPITALS
CLASSIFICATION

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Smeekens, S. P., Ng, A., Kumar, V., Johnson, M. D., Plantinga, T. S., van Diemen, C., Arts, P., Verwiel, E. T. P., Gresnigt, M. S., Fransen, K., van Sommeren, S., Oosting, M., Cheng, S.-C., Joosten, L. A. B., Hoischen, A., Kullberg, B.-J., Scott, W. K., Perfect, J. R., van der Meer, J. W. M., ... Xavier, R. J. (2013). Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans. Nature Communications, 4, Article 1342. https://doi.org/10.1038/ncomms2343

@article{49c94cecde5146dbaf4c22c5cd7a57d6,

title = "Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans",

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 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.",

keywords = "BLOOD-STREAM INFECTIONS, LISTERIA-MONOCYTOGENES, GENE-EXPRESSION, UNITED-STATES, RNA-SEQ, EPIDEMIOLOGY, RECOGNITION, MACROPHAGES, HOSPITALS, CLASSIFICATION",

author = "Smeekens, {Sanne P.} and Aylwin Ng and Vinod Kumar and Johnson, {Melissa D.} and Plantinga, {Theo S.} and {van Diemen}, Cleo and Peer Arts and Verwiel, {Eugene T. P.} and Gresnigt, {Mark S.} and Karin Fransen and {van Sommeren}, Suzanne and Marije Oosting and Shih-Chin Cheng and Joosten, {Leo A. B.} and Alexander Hoischen and Bart-Jan Kullberg and Scott, {William K.} and Perfect, {John R.} and {van der Meer}, {Jos W. M.} and Cisca Wijmenga and Netea, {Mihai G.} and Xavier, {Ramnik J.}",

year = "2013",

month = jan,

doi = "10.1038/ncomms2343",

language = "English",

volume = "4",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

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 2013, 'Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans', Nature Communications, vol. 4, 1342. https://doi.org/10.1038/ncomms2343

TY - JOUR

T1 - Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans

AU - Smeekens, Sanne P.

AU - Ng, Aylwin

AU - Kumar, Vinod

AU - Johnson, Melissa D.

AU - Plantinga, Theo S.

AU - van Diemen, Cleo

AU - Arts, Peer

AU - Verwiel, Eugene T. P.

AU - Gresnigt, Mark S.

AU - Fransen, Karin

AU - van Sommeren, Suzanne

AU - Oosting, Marije

AU - Cheng, Shih-Chin

AU - Joosten, Leo A. B.

AU - Hoischen, Alexander

AU - Kullberg, Bart-Jan

AU - Scott, William K.

AU - Perfect, John R.

AU - van der Meer, Jos W. M.

AU - Wijmenga, Cisca

AU - Netea, Mihai G.

AU - Xavier, Ramnik J.

PY - 2013/1

Y1 - 2013/1

N2 - 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.

AB - 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.

KW - BLOOD-STREAM INFECTIONS

KW - LISTERIA-MONOCYTOGENES

KW - GENE-EXPRESSION

KW - UNITED-STATES

KW - RNA-SEQ

KW - EPIDEMIOLOGY

KW - RECOGNITION

KW - MACROPHAGES

KW - HOSPITALS

KW - CLASSIFICATION

U2 - 10.1038/ncomms2343

DO - 10.1038/ncomms2343

M3 - Article

SN - 2041-1723

VL - 4

JO - Nature Communications

JF - Nature Communications

M1 - 1342

ER -

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

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Keywords

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