Candida Infection Biology – fungal armoury, battlefields ... - FINSysB
Candida Infection Biology – fungal armoury, battlefields ... - FINSysB
Candida Infection Biology – fungal armoury, battlefields ... - FINSysB
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Poster number: 35<br />
The Tyr238X dectin-1 polymorphism is a predisposing<br />
factor for mucosal <strong>Candida</strong> albicans infections but not<br />
candidemia<br />
Diana C. Rosentul 1,2 , Theo S. Plantinga 1,2 , Marije Oosting 1,2 , William K.<br />
Scott 3 , Digna R. Velez Edwards 4 , P. Brian Smith 5 , Barbara D. Alexander 5 ,<br />
John C. Yang 6 , Gregory M. Laird 5 , Walter J. F. M. van der Velden 2,7 , Bart<br />
Ferwerda 1,2 , Annemiek B. van Spriel 2,8 , Gosse Adema 2,8 , Ton Feuth 2,9 , J.<br />
Peter Donnelly 1,2 , Gordon D. Brown 10 , Nicole M. A. Blijlevens 2,7 , Leo A.B.<br />
Joosten 1,2 , Jos W. M. van der Meer 1,2 , John R. Perfect 5 , Bart-Jan Kullberg 1,2 ,<br />
Melissa D. Johnson 5,11 , Mihai G. Netea 1,2<br />
1 Department of Internal Medicine, Radboud University Nijmegen Medical Center, Nijmegen,<br />
The Netherlands; 2 Nijmegen Institute for <strong>Infection</strong>, Inflammation and Immunity (N4i), Radboud<br />
University Nijmegen Medical Center, Nijmegen, The Netherlands; 3 Dr. John T. Macdonald<br />
Foundation Department of Human Genetics and John P. Hussman Institute for Human<br />
Genomics, University of Miami, Miller School of Medicine, Miami, FL, USA; 4 Department of<br />
Obstetrics & Gynecology, Vanderbilt University Medical Center, Nashville, TN, USA; 5 Duke<br />
University Medical Center, Durham, NC, USA; 6 National Jewish Health, Denver, CO, USA;<br />
7 Department of Haematology, Radboud University Nijmegen Medical Center, Nijmegen, The<br />
Netherlands; 8 Department of Tumor Immunology, Radboud University Nijmegen Medical<br />
Center, Nijmegen, The Netherlands; 9 Department of Epidemiology, Biostatistics and Health<br />
Technology Assessment, Radboud University Nijmegen Medical Center, Nijmegen, The<br />
Netherlands; 10 Institute of Infectious Disease and Molecular Medicine, University of Cape<br />
Town, Cape Town, South Africa; 11 Department of Clinical Research, Campbell University<br />
School of Pharmacy, Buies Creek, NC, USA.<br />
The genetic make up of innate immune genes is believed to play an important role<br />
for susceptibility to <strong>fungal</strong> infections. We recently described the Tyr238X dectin-1<br />
single nucleotide polymorphism (SNP) as an important factor influencing<br />
susceptibility to vulvo-vaginal candidiasis and onychomycosis in a Dutch family<br />
with recurrent <strong>fungal</strong> infections.<br />
The aim of our studies was to assess the role of this polymorphism in the<br />
susceptibility to mucosal and systemic <strong>Candida</strong> albicans infections. To achieve this<br />
aim we have investigated the effect of this SNP in several cohorts of patients:<br />
-142 Dutch patients undergoing hematopoietic stem cells transplantation (HSCT).<br />
-331 Dutch and American candidemia patients and 351 non infected matched<br />
controls.<br />
Functional studies have shown that cells isolated from individuals heterozygous for<br />
the 238X allele had a lower cytokine production upon stimulation with <strong>Candida</strong>. The<br />
HSCT patients bearing the early stop variant of the dectin-1 gene presented a<br />
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