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Fungus-Specific CD4 T Cells as Specific Sensors for Identification of Pulmonary Fungal Infections

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Abstract

Patients with cystic fibrosis (CF) suffer from chronic lung infections, caused by bacterial, viral or fungal pathogens, which determine morbidity and mortality. The contribution of individual pathogens to chronic disease and acute lung exacerbations is often difficult to determine due to the complex composition of the lung microbiome in CF. In particular, the relevance of fungal pathogens in CF airways remains poorly understood due to limitations of current diagnostics to identify the presence of fungal pathogens and to resolve the individual host–pathogen interaction status. T-lymphocytes play an essential role in host defense against pathogens, but also in inappropriate immune reactions such as allergies. They have the capacity to specifically recognize and discriminate the different pathogens and orchestrate a diverse array of effector functions. Thus, the analysis of the fungus-specific T cell status of an individual can in principle provide detailed information about the identity of the fungal pathogen(s) encountered and the actual fungus–host interaction status. This may allow to classify patients, according to appropriate (protective) or inappropriate (pathology-associated) immune reactions against individual fungal pathogens. However, T cell-based diagnostics are currently not part of the clinical routine. The identification and characterization of fungus-specific T cells in health and disease for diagnostic purposes are associated with significant challenges. Recent technological developments in the field of fungus-specific T helper cell detection provide new insights in the host T cell–fungus interaction. In this review, we will discuss basic principles and the potential of T cell-based diagnostics, as well as the perspectives and further needs for use of T cells for improved clinical diagnostics of fungal diseases.

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Acknowledgements

This work was supported by financial grants from the Cystic Fibrosis Foundation (SCHEFF15G0), the German Federal Ministry of Education and Science (BMBF)–Project InfectControl 2020 (ART4Fun Fkz 03ZZ0813A), the Christiane Herzog Stiftung, Stuttgart, Germany and the Mukoviszidose e.V., Bonn, the German Cystic Fibrosis Association.

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Correspondence to Alexander Scheffold.

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Alexander Scheffold works as a consultant for Miltenyi Biotec who owns IP rights concerning parts of the ARTE technology. Carsten Schwarz and Petra Bacher have no conflict of interest to declare.

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Scheffold, A., Schwarz, C. & Bacher, P. Fungus-Specific CD4 T Cells as Specific Sensors for Identification of Pulmonary Fungal Infections. Mycopathologia 183, 213–226 (2018). https://doi.org/10.1007/s11046-017-0229-2

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