Abstract
Human fungal infections are a historically neglected area of disease research, yet they cause more than 1.5 million deaths every year. Our understanding of the pathophysiology of these infections has increased considerably over the past decade, through major insights into both the host and pathogen factors that contribute to the phenotype and severity of these diseases. Recent studies are revealing multiple mechanisms by which fungi modify and manipulate the host, escape immune surveillance and generate complex comorbidities. Although the emergence of fungal strains that are less susceptible to antifungal drugs or that rapidly evolve drug resistance is posing new threats, greater understanding of immune mechanisms and host susceptibility factors is beginning to offer novel immunotherapeutic options for the future. In this Review, we provide a broad and comprehensive overview of the pathobiology of human fungal infections, focusing specifically on pathogens that can cause invasive life-threatening infections, highlighting recent discoveries from the pathogen, host and clinical perspectives. We conclude by discussing key future challenges including antifungal drug resistance, the emergence of new pathogens and new developments in modern medicine that are promoting susceptibility to infection.
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The authors acknowledge funding from the MRC Centre for Medical Mycology at the University of Exeter (MR/N006364/2 and MR/V033417/1), the MRC and UKRI (MR/M026663/2, MR/V005731/1, MR/X014010/1 and MR/S001824/1), the Biotechnology and Biological Sciences Research Council (BB/V017004/1 and BB/W009625/1), the National Institute for Health and Care Research (NIHR) Exeter Biomedical Research Centre (BRC), the NIHR (NIHR134342 and NIHR303140), the Centers for Disease Control and Prevention (1NU51CK000315-01-00), the Royal Society (UF080611), the Wellcome Trust (217163, 102705, 225303, 101873, 200208, 215599, 224323, WT2049, 209293, 218550/Z/19/Z, 214317, 211241 and 206412), a Wellcome Trust Institutional Strategic Support Award (WT105618MA), the Lister Institute and an AMS Springboard Award SBF006/1024 (UK). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.
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W.H. has received research funding from the FDA; research funding and personal fees from F2G and Pfizer; and personal fees from GSK, Mundipharma and Pulmocide. T.S.H. has received an investigator award to institution from Gilead Sciences and speaker fees from Gilead and Pfizer and serves on Advisory or Data Monitoring Boards for F2G and Mundipharma. A.W. has received consultancy fees from Gilead and Mundipharma and payment for educational events from Gilead and F2G. The other authors declare no conflicts of interest.
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Brown, G.D., Ballou, E.R., Bates, S. et al. The pathobiology of human fungal infections. Nat Rev Microbiol (2024). https://doi.org/10.1038/s41579-024-01062-w
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DOI: https://doi.org/10.1038/s41579-024-01062-w
