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  • Review Article
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Aspergillus fumigatus biology, immunopathogenicity and drug resistance

Nature Reviews Microbiology volume 23, pages 652–666 (2025)Cite this article

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Abstract

Aspergillus fumigatus is a saprophytic fungus prevalent in the environment and capable of causing severe invasive infection in humans. This organism can use strategies such as molecule masking, immune response manipulation and gene expression alteration to evade host defences. Understanding these mechanisms is essential for developing effective diagnostics and therapies to improve patient outcomes in Aspergillus-related diseases. In this Review, we explore the biology and pathogenesis of A. fumigatus in the context of host biology and disease, highlighting virus-associated pulmonary aspergillosis, a newly identified condition that arises in patients with severe pulmonary viral infections. In the post-pandemic landscape, in which immunotherapy is gaining attention for managing severe infections, we examine the host immune responses that are critical for controlling invasive aspergillosis and how A. fumigatus circumvents these defences. Additionally, we address the emerging issue of azole resistance in A. fumigatus, emphasizing the urgent need for greater understanding in an era marked by increasing antimicrobial resistance. This Review provides timely insights necessary for developing new immunotherapeutic strategies against invasive aspergillosis.

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Fig. 1: Habitats and life cycles of Aspergillus fumigatus.
Fig. 2: Mechanisms of Aspergillus fumigatus adaptation to the host.
Fig. 3: Physiological innate immune response to Aspergillus fumigatus infection.
Fig. 4: Influenza-associated and COVID-19-associated pulmonary aspergillosis.
Fig. 5: Ability of Aspergillus fumigatus to generate genetic variation according to the reproduction mode, frequency and potential sites for resistance selection.

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Acknowledgements

F.L.vdV. is supported by the European Union Horizon 2020 (EU H2020) programme HDM-FUN (847507) and the Dutch Research Council and Netherlands Organisation for Health Research CAPA (10430102110011). G.C. is supported by European Union grants (European Research Council Consolidator Grant, iMAC-FUN (864957) and the EU H2020 programme HDM-FUN) and a National Grant (GSRI-11412, Pro-sCAP). A.C. is supported by the EU H2020 programme HDM-FUN and the Fundação para a Ciência e a Tecnologia, Portugal (UIDB/50026/2020, UIDP/50026/2020, LA/P/0050/2020 and PTDC/MED-OUT/1112/2021). We thank Simon Feys for helping with Fig. 3 and Matthaios Sertedakis for helping with Fig. 2.

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Authors and Affiliations

  1. Department of Internal Medicine, Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands

    Frank L. van de Veerdonk

  2. Radboudumc/CWZ Center of Expertise in Mycology (RCEM), Radboud University Medical Center, Nijmegen, The Netherlands

    Frank L. van de Veerdonk & Paul E. Verweij

  3. Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal

    Agostinho Carvalho

  4. ICVS/3B’s–PT Government Associate Laboratory, Braga, Portugal

    Agostinho Carvalho

  5. Medical Intensive Care, University Hospitals Leuven and Department for Clinical Infectious and Inflammatory Disorders, University Leuven, Leuven, Belgium

    Joost Wauters

  6. Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Heraklion, Greece

    George Chamilos

  7. School of Medicine, University of Crete, Heraklion, Greece

    George Chamilos

  8. Department of Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands

    Paul E. Verweij

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van de Veerdonk, F.L., Carvalho, A., Wauters, J. et al. Aspergillus fumigatus biology, immunopathogenicity and drug resistance. Nat Rev Microbiol 23, 652–666 (2025). https://doi.org/10.1038/s41579-025-01180-z

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