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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Rosentul, DC; Plantinga, TS; Oosting, M; Scott, WK; Velez Edwards, DR; Smith, PB; Alexander, BD; Yang, JC; Laird, GM; Joosten, LAB; van der Meer, JWM; Perfect, JR; Kullberg, B-J; Netea, MG; Johnson, MD

Published Date

  • October 1, 2011

Published In

Volume / Issue

  • 204 / 7

Start / End Page

  • 1138 - 1145

PubMed ID

  • 21881131

Electronic International Standard Serial Number (EISSN)

  • 1537-6613

Digital Object Identifier (DOI)

  • 10.1093/infdis/jir458

Language

  • eng

Conference Location

  • United States