Calprotectin Against Life-Threatening Moulds

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Calprotectin Against Life-Threatening Moulds

http://insciences.org/article.php?article_id=9984

An infection with the mould " Aspergillus " often kills patients with chronic

granulomatous disease (CGD). Researchers from the University of Zurich and the

University Children's Hospital Zurich shows now, that calprotectin is a key

player for the immune defence against infection with " Aspergillus " . The study

may eventually lead to a new treatment modality of CGD patients.

Fungal infections with moulds can cause life-threatening health problems in

patients with chronic neutropenia, or neutrophil dysfunction such as chronic

granulomatous disease (CGD). CGD is a genetic severe immune deficiency disease

that occurs at a frequency of one in 70,000 newborns per year worldwide.

Children with CGD often suffer from life-threatening microbial infections with

bacteria and moulds, due to a defect in phagocyte NADPH oxidase. Particularly,

infections with Aspergillus spp. often kill CGD patients, before bone marrow

transplantation or gene therapy can be performed. While healthy individuals'

white blood cells, also called neutrophils, release reactive oxygen species by

action of the NADPH oxidase to kill and digest invading pathogens, the

neutrophils in CGD patients lack the ability to kill these microbes.

Janine Reichenbach, consultant in Clinical Immunology and research group leader

at the Division of Immunology/Haematology/BMT, University Children's Hospital

Zurich is studying mechanisms of innate immunity against infections. In earlier

studies, in collaboration with Prof. A. Zychlinsky's group at the Max Planck

Institute for Infection Biology, Berlin, Germany, her group found that normal

neutrophils form extracellular structures, called neutrophil extracellular traps

or NETs, which catch and trap Aspergillus fungi for efficient control of

infection. NETs are web-like structures made of chromatin and decorated with

antimicrobial proteins.

In collaboration with researchers at the Umeå University in Sweden, the

scientists from University Children's Hospital in Zurich found new details

behind CGD. They compared the function of a CGD patient's neutrophils before and

after gene therapy, performed at the University Children's Hospital in Zurich.

" Our results clearly show that the antimicrobial calprotectin released within

NETs is also important for the neutrophils immune defence against Aspergillus

infection, " says Janine Reichenbach.

Together with PhD student Matteo Bianchi in her group at University Children's

Hospital Zurich and researchers in Umeå, Janine Reichenbach found that

neutrophils from the CGD patient did not form NETs and were not able to release

calprotectin before gene therapy. Therefore neutrophils were not able to kill

and digest Aspergillus. " We found that after gene therapy corrected neutrophils

could release calprotectin and the NET structure, " says Matteo Bianchi. " Our

experiment showed that calprotectin is a key player for the neutrophils' defence

against Aspergillus infection.

" Our mechanistic study may eventually lead to a new treatment modality of CGD

patients and prevent them from fungal infections until they have the possibility

to receive gene therapy or bone marrow transplantation, which are more

sustainable treatments, " says Janine Reichenbach.

Publication:

Bianchi Matteo, Niemiec J., Siler Ulrich, Urban Constantin F., Reichenbach

Janine.: Restoration of anti-Aspergillus defense by neutrophil extracellular

traps in human chronic granulomatous disease after gene therapy is

calprotectin-dependent. Journal of Allergy and Clinical Immunology. doi:

10.1016/j.jaci.2011.01.021

Contact: Beat Müller, Media Officer, Tel: +41 44 634 44 32, Email:

beat.mueller@...

Source: University of Zurich