ALLFUN

"Fungi in the setting of inflammation, allergy and autoimmune diseases:Translating basic science into clinical practices"

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 Obiettivo del progetto (Objective)

'The ALLFUN proposal aims at defining the cellular and molecular mechanisms by which ubiquitous airborne or commensal fungi contribute to immune homeostasis and its dysregulation leading to allergy and inflammatory diseases. Breakthroughs in understanding how mucosal homeostasis is established, maintained or disrupted in the presence of fungi should be sources of new therapeutic targets and drugs (i.e. anti-inflammatory, immunomodulatory and anti-infectious molecules). European scientists representing the leading edge of this field are brought together here in a unique synergistic and cross-cutting collaboration that addresses a major medical and economic problem of considerable importance to the health care sector. The study will be centered on yeasts and filamentous fungi known to be associated with a number of inflammatory, autoimmune and allergic diseases. Via a multidisciplinary systems biology study combining fungal genetics, clinical research and animal models in a systems biology approach, integrating traditional wet-lab methods with those of functional genomics, immunomics, allergomics and bioinformatics, the ALLFUN project meets the criteria of the call, the strategic objective of which is “to elucidate mechanisms by which infections may lead to aberrant activation of inflammation, the lack of resolution of which is responsible for inflammatory diseases”. The anticipated results are highly relevant to society in terms of reducing the burden of mortality and suffering in patients with fungus-related diseases, identifying more accurate biomarkers for immunological disorders, optimizing and possibly reducing the cost of antifungal therapy by association with anti-inflammatory strategies that targets pathogenicity rather than microbial growth, the host-pathogen interface rather than the pathogen. Understanding the spectrum of immunological responses to fungi is perhaps the single most important challenge in the field of medical mycology.'

Introduzione (Teaser)

The fungi kingdom comprises over 1.5 million species, and yet only a handful of these are associated with disease, ranging from allergy and autoimmunity to life-threatening infections. Delineating the underlying immune mechanisms that lead to fungal disease is the subject of the Allfun project.

Descrizione progetto (Article)

Fungi can reside on human skin and body cavities without causing disease. The most serious human diseases caused by fungi are the opportunistic fungal infections that occur in patients with defective immunity. This clearly indicates that underlying deregulated inflammatory responses are responsible for disease susceptibility.

Understanding how mucosal homeostasis is established, maintained or disrupted in the presence of fungi could lead to the identification of new therapeutic targets and drugs. The EU-funded Allfun project is studying the specific cellular and molecular mechanisms by which ubiquitous airborne or commensal fungi contribute to immune homeostasis and how immune deregulation leads to inflammatory diseases.

The study is centred on yeasts and filamentous fungi known to be associated with various inflammatory, autoimmune and allergic diseases. Work in experimental models of fungal allergy and mucosal inflammation has led to the identification of certain fungal molecules, the so-called tissue damage-associated molecular patterns (DAMPs) that work down specific signalling pathways. The identification of such immunogenic molecules will lead to the development of ultrasensitive diagnostic kits and new targets for therapy.

Another objective of the study is to delineate the complex interaction between immune cell pattern recognition receptors (PRRs) and fungal pathogen-associated molecular patterns (PAMPs). This will help the characterisation of the recognition phenomena leading to innate and adaptive immunity responses towards fungi.

Genetic association studies on high-risk individuals have resulted in the discovery of several single nucleotide polymorphisms (SNPs) implicated in inflammatory fungal diseases. The identification of susceptibility genes in high-risk patients will improve risk stratification, optimise therapy and favour personalised treatment options.

An important achievement with direct clinical applicability is the identification of a tryptophan metabolic measurement which acts as a good indicator of the patient's ability to cope with fungus-driven inflammation. Partners are proposing that the tryptophan metabolite kynurenine could have an immunomodulatory function in patients.

Collectively, the knowledge acquired during the Allfun project could well contribute towards the design and validation of intervention strategies that target fungi-mediated allergy and inflammation.