Role of Proinflammatory Fungal Lipoids in Fungal Inflammation

• Applicant: Professor Dr. Jens-Michael Schröder
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2004 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5427513

Polymorphonuclear leukocytes represent primary components of the host's innate immune defenses against fungal infection suggesting involvement of fungal leukocyte attractants and proinflammatory cytokines. We found in various fungi, but not in bacteria or host cells, unstable lipid-like leukocyte chemoattractants. Purification from yeast, structural analyses and chemical synthesis revealed these inflammatory mediators as members of a novel familiy of lipoids, which activate neutrophils via putative, G-protein-coupled receptors. It is the aim of this project to investigate the role of these unstable lipids in fungal inflammation, in particular to identify these lipoids by mass spectrometry in different pathogenic fungi and to investigate conditions of its production. We further observed, that yeast lipid extracts induced proinflammatory cytokines and the chemokines Interleukin-8 and RANTES in keratinocytes. Preliminary investigations showed, that these lipoids appear at least in part to be structurally different from leukocyte-activating lipoids. Therefore it is a further aim to elucidate the molecular nature of these cytokine-inducing fungal lipoids and to identify its putative cellular receptors. These fungus-specific lipoids, its host cell receptors and possibly the enzymes involved in its biosynthesis may be targets for a novel anti-inflammatory therapy in fungal infection.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1160: Colonisation and Infection by Human-pathogenic Fungi