Candida Infection Biology – fungal armoury, battlefields ... - FINSysB

The Tyr238X dectin-1 polymorphism is a predisposing
factor for mucosal Candida albicans infections but not
candidemia
Diana C. Rosentul 1,2 , Theo S. Plantinga 1,2 , Marije Oosting 1,2 , William K.
Scott 3 , Digna R. Velez Edwards 4 , P. Brian Smith 5 , Barbara D. Alexander 5 ,
John C. Yang 6 , Gregory M. Laird 5 , Walter J. F. M. van der Velden 2,7 , Bart
Ferwerda 1,2 , Annemiek B. van Spriel 2,8 , Gosse Adema 2,8 , Ton Feuth 2,9 , J.
Peter Donnelly 1,2 , Gordon D. Brown 10 , Nicole M. A. Blijlevens 2,7 , Leo A.B.
Joosten 1,2 , Jos W. M. van der Meer 1,2 , John R. Perfect 5 , Bart-Jan
Kullberg 1,2 , Melissa D. Johnson 5,11 , Mihai G. Netea 1,2
1 Department of Internal Medicine, Radboud University Nijmegen Medical Center, Nijmegen,
The Netherlands; 2 Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud
University Nijmegen Medical Center, Nijmegen, The Netherlands; 3 Dr. John T. Macdonald
Foundation Department of Human Genetics and John P. Hussman Institute for Human
Genomics, University of Miami, Miller School of Medicine, Miami, FL, USA; 4 Department of
Obstetrics & Gynecology, Vanderbilt University Medical Center, Nashville, TN, USA; 5 Duke
University Medical Center, Durham, NC, USA; 6 National Jewish Health, Denver, CO, USA;
7 Department of Haematology, Radboud University Nijmegen Medical Center, Nijmegen, The
Netherlands; 8 Department of Tumor Immunology, Radboud University Nijmegen Medical
Center, Nijmegen, The Netherlands; 9 Department of Epidemiology, Biostatistics and Health
Technology Assessment, Radboud University Nijmegen Medical Center, Nijmegen, The
Netherlands; 10 Institute of Infectious Disease and Molecular Medicine, University of Cape
Town, Cape Town, South Africa; 11 Department of Clinical Research, Campbell University
School of Pharmacy, Buies Creek, NC, USA.
The genetic make up of innate immune genes is believed to play an important role
for susceptibility to fungal infections. We recently described the Tyr238X dectin-1
single nucleotide polymorphism (SNP) as an important factor influencing
susceptibility to vulvo-vaginal candidiasis and onychomycosis in a Dutch family
with recurrent fungal infections.
The aim of our studies was to assess the role of this polymorphism in the
susceptibility to mucosal and systemic Candida albicans infections. To achieve this
aim we have investigated the effect of this SNP in several cohorts of patients:
-142 Dutch patients undergoing hematopoietic stem cells transplantation (HSCT).
-331 Dutch and American candidemia patients and 351 non infected matched
controls.
Functional studies have shown that cells isolated from individuals heterozygous for
the 238X allele had a lower cytokine production upon stimulation with Candida. The
HSCT patients bearing the early stop variant of the dectin-1 gene presented a
higher C. albicans oral an gastrointestinal colonization compared to those who were
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