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 M. Laird, Leo A.B. Joosten, Jos W.M. Van Der Meer, John R. Perfect, Bart Jan Kullberg, Mihai G. Netea, Melissa D. Johnson

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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

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Rosentul, D. C., Plantinga, T. S., Oosting, M., Scott, W. K., Velez Edwards, D. R., Smith, P. B., Alexander, B. D., Yang, J. C., Laird, G. M., Joosten, L. A. B., Van Der Meer, J. W. M., Perfect, J. R., Kullberg, B. J., Netea, M. G., & 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