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signal mechanism in fungal infections identified

(Vienna, 10 February 2011) A current project of the Medical University of Vienna is decoding a new signalling pathway in immune cells that allows otherwise harmless fungi to trigger severe infections. The targeted manipulation of these signal pathways could give rise to new therapeutic approaches aimed at detecting fungal infections early on and thereby improving the chances of a cure.

Yeast fungi from the Candida family are part of the normal microbial flora of the gut and the mucous membrane. Occasionally, these fungi can cause superficial and non-threatening infections in healthy individuals. If the immune system is weakened, however, such as in patients on intensive care units or patients who have had transplants, Candida yeasts can cause invasive infections with a high mortality rate of more than 40%.

These fungi are detected by the immune system in various ways, but one of them is dendritic cells, which also control the body’s appropriate immune response. The research group led by Associate Professor Dr. Karl Kuchler of the Department of Molecular Genetics at MedUni Vienna has discovered a previously unknown signal transfer pathway in dendritic cells that is activated by the detection of Candida fungi. This signal pathway triggers the release of cytokines and transmitters (known as type I interferons) that otherwise cause a protective immune defence, especially with viral infections. With Candida infections, the activation of this pathway however damages the host, since these highly active transmitters also attack healthy tissue and therefore lead to inflammatory organ damage. What’s more, the fungal pathogen may remain in the affected organ for a long period of time.

This discovery and decoding of the importance of this signal pathway for the progression of invasive fungal infections in humans could therefore facilitate the development of new therapeutic approaches so that, in future, fatal fungal infections can be spotted earlier and therefore treated more effectively.

The work has been published in the current edition of the highly-respective “Journal of Immunology”, and was carried out in the Christian Doppler Laboratory for Infection Biology at the Max. F. Perutz Laboratories (MFPL) of MedUni Vienna. The work was performed in collaboration with Thomas Decker's working groups at the University of Vienna and Mathias Müller from Biomodels Austria, Centre for Biomodels at the University of Veterinary Medicine of Vienna.

» Publication in "Journal of Immunology":
Conventional Dendritic Cells Mount a Type I IFN Response against Candida spp. Requiring Novel Phagosomal TLR7-Mediated IFN-{beta} Signaling.
Bourgeois C, Majer O, Frohner IE, Lesiak-Markowicz I, Hildering KS, Glaser W, Stockinger S, Decker T, Akira S, Müller M, Kuchler K.
J Immunol. 186: 2011 Jan 31. Epub ahead of print

Key: Mouse kidney infected with Candida albicans fungal hyphae (purple) surrounded by infiltrating immune cells (dark blue) that are attacking and eliminating the Candida hyphae - Histopathology in collaboration with Professor Dontscho Kerjaschki of the Clinical Institute of Pathology at the Medical University of Vienna.