Genetic variation in the dectin-1/CARD9 recognition pathway and susceptibility to candidemia

Diana C. Rosentul, Theo S. Plantinga, Marije Oosting, William K. Scott, Digna R. Velez Edwards, P. Brian Smith, Barbara D. Alexander, John C. Yang, Gregory Laird, Leo A B Joosten, Jos W M Van Der Meer, John R. Perfect, Bart Jan Kullberg, Mihai G. Netea, Melissa D. Johnson

Research output: Contribution to journalArticle

Abstract

Background. Candidemia is an important cause of morbidity and mortality in critically ill patients or patients undergoing invasive treatments. Dectin-1 is the main β-glucan receptor, and patients with a complete deficiency of either dectin-1 or its adaptor molecule CARD9 display persistent mucosal infections with Candida albicans. The role of genetic variation of DECTIN-1 and CARD9 genes on the susceptibility to candidemia is unknown. Methods. We assessed whether genetic variation in the genes encoding dectin-1 and CARD9 influence the susceptibility to candidemia and/or the clinical course of the infection in a large cohort of American and Dutch candidemia patients (n = 331) and noninfected matched controls (n = 351). Furthermore, functional studies have been performed to assess the effect of the DECTIN-1 and CARD9 genetic variants on cytokine production in vitro and in vivo in the infected patients. Results. No significant association between the single-nucleotide polymorphisms DECTIN-1 Y238X and CARD9 S12N and the prevalence of candidemia was found, despite the association of the DECTIN-1 238X allele with impaired in vitro and in vivo cytokine production. Conclusions. Whereas the dectin-1/CARD9 signaling pathway is nonredundant in mucosal immunity to C. albicans, a partial deficiency of β-glucan recognition has a minor impact on susceptibility to candidemia.

Original languageEnglish (US)
Pages (from-to)1138-1145
Number of pages8
JournalJournal of Infectious Diseases
Volume204
Issue number7
DOIs
StatePublished - Oct 1 2011
Externally publishedYes

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Candidemia
Glucans
Candida albicans
Cytokines
Mucosal Immunity
Infection
Critical Illness
Genes
Single Nucleotide Polymorphism
dectin 1
Alleles
Morbidity
Mortality

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Rosentul, D. C., Plantinga, T. S., Oosting, M., Scott, W. K., Velez Edwards, D. R., Smith, P. B., ... Johnson, M. D. (2011). Genetic variation in the dectin-1/CARD9 recognition pathway and susceptibility to candidemia. Journal of Infectious Diseases, 204(7), 1138-1145. https://doi.org/10.1093/infdis/jir458

Genetic variation in the dectin-1/CARD9 recognition pathway and susceptibility to candidemia. / Rosentul, Diana C.; Plantinga, Theo S.; Oosting, Marije; Scott, William K.; Velez Edwards, Digna R.; Smith, P. Brian; Alexander, Barbara D.; Yang, John C.; Laird, Gregory; Joosten, Leo A B; Van Der Meer, Jos W M; Perfect, John R.; Kullberg, Bart Jan; Netea, Mihai G.; Johnson, Melissa D.

In: Journal of Infectious Diseases, Vol. 204, No. 7, 01.10.2011, p. 1138-1145.

Research output: Contribution to journalArticle

Rosentul, DC, Plantinga, TS, Oosting, M, Scott, WK, Velez Edwards, DR, Smith, PB, Alexander, BD, Yang, JC, Laird, G, Joosten, LAB, Van Der Meer, JWM, Perfect, JR, Kullberg, BJ, Netea, MG & Johnson, MD 2011, 'Genetic variation in the dectin-1/CARD9 recognition pathway and susceptibility to candidemia', Journal of Infectious Diseases, vol. 204, no. 7, pp. 1138-1145. https://doi.org/10.1093/infdis/jir458
Rosentul DC, Plantinga TS, Oosting M, Scott WK, Velez Edwards DR, Smith PB et al. Genetic variation in the dectin-1/CARD9 recognition pathway and susceptibility to candidemia. Journal of Infectious Diseases. 2011 Oct 1;204(7):1138-1145. https://doi.org/10.1093/infdis/jir458
Rosentul, Diana C. ; Plantinga, Theo S. ; Oosting, Marije ; Scott, William K. ; Velez Edwards, Digna R. ; Smith, P. Brian ; Alexander, Barbara D. ; Yang, John C. ; Laird, Gregory ; Joosten, Leo A B ; Van Der Meer, Jos W M ; Perfect, John R. ; Kullberg, Bart Jan ; Netea, Mihai G. ; Johnson, Melissa D. / Genetic variation in the dectin-1/CARD9 recognition pathway and susceptibility to candidemia. In: Journal of Infectious Diseases. 2011 ; Vol. 204, No. 7. pp. 1138-1145.
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AU - Rosentul, Diana C.

AU - Plantinga, Theo S.

AU - Oosting, Marije

AU - Scott, William K.

AU - Velez Edwards, Digna R.

AU - Smith, P. Brian

AU - Alexander, Barbara D.

AU - Yang, John C.

AU - Laird, Gregory

AU - Joosten, Leo A B

AU - Van Der Meer, Jos W M

AU - Perfect, John R.

AU - Kullberg, Bart Jan

AU - Netea, Mihai G.

AU - Johnson, Melissa D.

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N2 - Background. Candidemia is an important cause of morbidity and mortality in critically ill patients or patients undergoing invasive treatments. Dectin-1 is the main β-glucan receptor, and patients with a complete deficiency of either dectin-1 or its adaptor molecule CARD9 display persistent mucosal infections with Candida albicans. The role of genetic variation of DECTIN-1 and CARD9 genes on the susceptibility to candidemia is unknown. Methods. We assessed whether genetic variation in the genes encoding dectin-1 and CARD9 influence the susceptibility to candidemia and/or the clinical course of the infection in a large cohort of American and Dutch candidemia patients (n = 331) and noninfected matched controls (n = 351). Furthermore, functional studies have been performed to assess the effect of the DECTIN-1 and CARD9 genetic variants on cytokine production in vitro and in vivo in the infected patients. Results. No significant association between the single-nucleotide polymorphisms DECTIN-1 Y238X and CARD9 S12N and the prevalence of candidemia was found, despite the association of the DECTIN-1 238X allele with impaired in vitro and in vivo cytokine production. Conclusions. Whereas the dectin-1/CARD9 signaling pathway is nonredundant in mucosal immunity to C. albicans, a partial deficiency of β-glucan recognition has a minor impact on susceptibility to candidemia.

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