TY  - EJOU
AU  - Graaf, Chantal A. A. Van der 
AU  - Netea, Mihai G. 
AU  - Morré, Servaas A. 
AU  - Heijer, Martin Den 
AU  - Verweij, Paul E. 
AU  - Meer, Jos W. M. Van der 
AU  - Kullberg, Bart Jan 

TI  - Toll-like receptor 4 Asp299Gly/Thr399Ile polymorphisms are a risk factor for <i>Candida</i> bloodstream infection
T2  - European Cytokine Network

PY  - 2006
VL  - 17
IS  - 1
SN  - 1952-4005

AB  - Toll-like receptor (TLR)-4 is an important pattern recognition receptor for <i>Candida albicans</i>,
playing a role in innate host defense. We investigated whether there is an association between the TLR4 Asp299Gly
or TLR4 Thr399Ile polymorphism, and the occurrence of <i>Candida</i> bloodstream infection. We performed a
case-control study, involving 43 patients with a <i>Candida</i> bloodstream infection and 166 healthy individuals. TLR4
Asp299Gly and Thr399Ile polymorphisms were assessed, as well as cytokine production after stimulation of
peripheral blood mononuclear cells (PBMC) with <i>Candida albicans</i>. We observed that the prevalence of TLR4
Asp299Gly polymorphism was found to be higher in patients with <i>Candida</i> bloodstream infection than in controls
(26% versus 10%; OR 3.0; 95%CI 1.3-6.9). All patients bearing the Asp299Gly polymorphism were also positive
for the Thr399Ile allele, a linkage well described in literature. IL-10 production was higher in <i>C. albicans</i>-stimulated
PBMC from volunteers bearing the TLR4 Asp299Gly polymorphism, and a similar tendency was
observed in TLR4 Asp299Gly heterozygous patients who had recovered from candidemia. These findings show
that the TLR4 Asp299Gly/Thr399Ile polymorphisms are associated with an increased susceptibility to <i>Candida</i>
bloodstream infections, and an increased production of IL-10 is probably involved in this effect.
KW  - TLR4 polymorphism
KW  -  <i>Candida</i>
KW  -  bloodstream infection
KW  -  susceptibility
KW  -  cytokine

DO  -