Human Dectin-1 Deficiency and Mucocutaneous Fungal Infections

By B. Ferwerda, G. Ferwerda, T. Plantinga, J. Willment, A. V. van Spriel, H. Venselaar, C. Elbers, Melissa D. Johnson, A. Cambi, Cristal Huysamen and 15 more. New England Journal of Medicine, 2009

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SUMMARY Mucocutaneous fungal infections are typically found in patients who have no known immune defects. We describe a family in which four women who were affected by either recurrent vulvovaginal candidiasis or onychomycosis had the early-stop-codon mutation Tyr238X in the β-glucan receptor dectin-1. The mutated form of dectin-1 was poorly expressed, did not mediate β-glucan binding, and led to defective production of cytokines (interleukin-17, tumor necrosis factor, and interleukin-6) after stimulation with β-glucan or Candida albicans. In contrast, fungal phagocytosis and fungal killing were normal in the patients, explaining why dectin-1 deficiency was not associated with invasive fungal infections and highlighting the specific role of dectin-1 in human mucosal antifungal defense.

Subfields: Epidemiology, Infectious Diseases, Plant Science

View Paper: https://www.semanticscholar.org/paper/c6e8e307c76c2b708f0cc3e108f12f9a5c9cfcb2

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Citations in the corpus

Activation of the innate immune receptor Dectin-1 upon formation of a “phagocytic synapse” (2011, methodology): “7 macrophages stably expressing SBPc-tagged-Dectin-1 were incubated for 2 h at 37 uC with 100mg ml(21) unlabelled MMW soluble b-glucan, and binding was detected by flow cytometry using a mouse IgM monoclonal antibody specific forb-(1,3)-linked glucan (BfD IV; clone 10C6; ref.”
Candida albicans morphogenesis and host defence: discriminating invasion from colonization (2011, neutral): “, together with the discovery that host mutations in dectin 1 or CARD9 lead to primary immunodeficiencies associated with fungal infection”
mTOR- and HIF-1α–mediated aerobic glycolysis as metabolic basis for trained immunity (2014, background): “Monocytes isolated from patients with a complete deficiency in dectin-1 (23) failed to activate mTOR upon stimulation with b-glucan (Fig.”
Innate Immune Pattern Recognition: A Cell Biological Perspective (2015, neutral): “The major ligands for Dectin-1 are fungal β-1,3-glucans, and both mice and human studies confirmed a crucial role for this receptor in antifungal defense (123, 124).”
Candida albicans Infection Affords Protection against Reinfection via Functional Reprogramming of Monocytes (2012, background): “Inhibition of dectin-1 with laminarin inhibited the priming by β-glucans (Figure S2), and monocytes isolated from a dectin-1-deficient individual (Ferwerda et al., 2009) could not be effectively trained with β-glucan (Figure 3A).”
Dectin-1 is an extracellular pathogen sensor for the induction and processing of IL-1β via a noncanonical caspase-8 inflammasome (2012, background): “Dectin-1 deficiency in humans causes hypersusceptibility to mucocutaneous fungal infectio”
Dectin-2 recognition of alpha-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans. (2010, background): “Furthermore, it was recently reported that Dectin-1 is important for the defense against mucocutaneous fungal infection (Ferwerda et al., 2009).”
INTERLEUKIN-4- AND INTERLEUKIN-13-MEDIATED ALTERNATIVELY ACTIVATED MACROPHAGES: ROLES IN HOMEOSTASIS AND DISEASE (2013, neutral): “Dectin-1 (Clec7a) is an AAM-associated CLR that is expressed on macrophages, neutrophils, and DCs, among other cells, and is increasingly recognized as the principal PRR in mediating fungal recognition in mice (78, 79) and humans (80).”