Genetic links to fungal infection risk identified

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Genetic links to fungal infection risk identified 

http://www.eurekale rt.org/pub_ releases/ 2009-10/ucl- glt102809. php 

 

 

Two genetic mutations that may put individuals at increased risk of fungal

infections have been identified by scientists from UCL and Radboud University,

increasing understanding about the genetic basis of these infections and

potentially aiding the development of new treatments.

 

The two separate studies, published today in the New England Journal of

Medicine, mark a significant step in the understanding of genetic susceptibility

to fungal diseases. The findings have implications for people suffering from

chronic mucocutaneous candidiasis (CMC), as well as more common infections like

vaginal candidosis (thrush).

 

The UCL-led research focused on patients from multiple generations of a large

family who had suffered from serious recurrent fungal infections that proved

lethal in some of those affected. DNA sequencing and genetic mapping techniques

enabled the researchers to identify that this family had a recurrent mutation in

a gene called CARD9. The team from Radboud University in the Netherlands

discovered that a mutation in the gene Dectin-1 is associated with increased

susceptibility to vaginal infections by fungi (primarily of the genus Candida).

 

When these two genes are working correctly, Dectin-1 senses the presence of

fungi and prompts the immune cells to send signals that result in CARD9 setting

off a molecular response in the immune system to protect against these

microorganisms. If Dectin-1 or CARD9 are mutated or missing, the immune system

struggles to control Candida and may allow local or even systemic (affecting the

entire body) infections to develop.

 

Both studies involved researchers from across the world. Critical experiments to

prove the causality of the CARD9 mutation were done at the Technical University

of Munich, Germany, where mice lacking the corresponding gene had been shown to

be susceptible to fungal infections. Similarly, demonstration of the molecular

mechanisms leading to the loss of fungi recognition by mutated Dectin-1 in mice

had been performed by the University of Aberdeen.

 

Professor Mihai Netea, who led the team from Radboud University, said: " Although

the process of host response to fungal infection has previously been studied in

mice, it is very interesting to see that it is the same in humans. The new

results show that the mechanisms to protect against fungal infections have been

largely conserved by evolution between mice and humans, which is not necessarily

the case for other microbes. "

 

Corresponding author Professor Bodo Grimbacher, UCL Infection & Immunity and

Consultant Immunologist at The Royal Free Hospital, said: " This discovery

enables further insights in the interaction between fungi and the human immune

system and may pave the way for future therapeutic options in patients suffering

from Candida infections. "

 

###

Both studies accessed a variety of biological database resources at the National

Center for Biotechnology Information (NCBI), part of the National Library of

Medicine at the National Institutes of Health (United States). Dr

Schaffer, a researcher at NCBI and a co-author on the UCL paper, helped identify

CARD9 as the mutated gene.

 

Notes for Editors

1.) For more information, or to interview the UCL researcher quoted, please

contact Ruth Howells in the UCL Media Relations Office on tel: +44 (0)20 7679

9739, mobile: +44 (0)7990 675 947, out of hours +44 (0)7917 271 364, e-mail:

ruth.howells@ ucl.ac.uk

 

2.) The UCL paper 'Susceptibility to fungal infections due to homozygous

mutation in CARD9' is published in the latest edition of the NEJM. For copies of

the paper, please contact the NEJM press office on tel: +1-781-434-7847, or

email: mediasupport@ nejm.org.

 

3.) The Marie-Curie Excellence Research Group at UCL, under the guidance of

Professor Grimbacher, specialises in inborn errors of the human immune system.

Professor Netea's research group at Radboud University specialises in how the

human immune system defends itself against fungal infections.

 

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