IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-65262-5.html
   My bibliography  Save this article

High expression of interleukin-18 receptor alpha correlates with severe respiratory viral disease and defines T cells with reduced cytotoxic signatures

Author

Listed:
  • Aira F. Cabug

    (at the Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne)

  • Jeremy Chase Crawford

    (St. Jude Children’s Research Hospital, Department of Host-Microbe Interactions
    St. Jude Children’s Research Hospital, Center for Infectious Diseases Research)

  • Hayley A. McQuilten

    (at the Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne)

  • Isabelle J. H. Foo

    (at the Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne)

  • Lilith F. Allen

    (at the Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne)

  • Deborah Gebregzabher

    (at the Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne)

  • Robert C. Mettelman

    (St. Jude Children’s Research Hospital, Department of Host-Microbe Interactions)

  • Tanya Novak

    (Harvard Medical School, Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children’s Hospital and Department of Anaesthesia)

  • Janet Chou

    (Harvard Medical School, Division of Immunology, Boston Children’s Hospital)

  • Louise C. Rowntree

    (at the Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne)

  • Ruth R. Hagen

    (at the Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne)

  • Abby J. Thomson

    (at the Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne)

  • Genevieve E. Martin

    (at the Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne
    Austin Health, Department of Infectious Diseases)

  • Brad Gilbertson

    (at the Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne)

  • Michael NT Souter

    (at the Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne)

  • Fiona James

    (Austin Health, Department of Infectious Diseases)

  • Emma Goodall

    (Austin Health, Department of Infectious Diseases)

  • Simone Rizzetto

    (UNSW Sydney, School of Medical Sciences and The Kirby Institute)

  • Tim Flerlage

    (The University of Tennessee Health Science Center, Department of Pediatrics)

  • Xiaoxiao Jia

    (at the Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne)

  • Lee-Ann Van de Velde

    (St. Jude Children’s Research Hospital, Department of Host-Microbe Interactions)

  • So Young Chang

    (at the Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne)

  • Fabio Luciani

    (UNSW Sydney, School of Medical Sciences and The Kirby Institute)

  • Ryan S. Thwaites

    (Imperial College London, National Heart and Lung Institute)

  • Jason A. Trubiano

    (Peter MacCallum Cancer Centre, Department of Infectious Diseases
    Peter McCallum Cancer Centre, National Centre for Infections in Cancer
    University of Melbourne, Department of Medicine (Austin Health)
    Austin Health, Centre for Antibiotic Allergy and Research, Department of Infectious Diseases)

  • Tom C. Kotsimbos

    (The Alfred Hospital, Department of Respiratory Medicine
    Monash University, Department of Medicine, Central Clinical School, The Alfred Hospital)

  • Allen C. Cheng

    (Monash University, School of Public Health and Preventive Medicine
    Monash University, Monash Infectious Diseases, Monash Health and School of Clinical Sciences)

  • Adrienne G. Randolph

    (Harvard Medical School, Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children’s Hospital and Department of Anaesthesia
    Center for Influenza Disease and Emergence Response (CIDER))

  • Paul G. Thomas

    (St. Jude Children’s Research Hospital, Department of Host-Microbe Interactions
    Center for Influenza Disease and Emergence Response (CIDER))

  • Jianqing Xu

    (Fudan University, Shanghai Public Health Clinical Centre and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College)

  • Zhongfang Wang

    (at the Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne
    Guangzhou Medical University, State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University)

  • Thi H. O. Nguyen

    (at the Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne)

  • Brendon Y. Chua

    (at the Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne)

  • Lukasz Kedzierski

    (at the Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne)

  • Katherine Kedzierska

    (at the Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne
    Center for Influenza Disease and Emergence Response (CIDER))

Abstract

Hyperactivated immunity underpins severe outcomes of respiratory viral infections, yet specific immune perturbations are ill-defined. Our recent findings identified OLAH (oleoyl-ACP-hydrolase) as a driver of life-threatening viral diseases. In the same patient cohorts, we now identify the gene encoding IL-18Rα chain (IL18R1), as being highly expressed in life-threatening influenza, COVID-19, RSV and multisystem inflammatory syndrome in children (MIS-C) and demonstrate markedly elevated surface protein IL-18Rα expression on CD8 T cells in these infections. Using a mouse model of severe influenza, we further show that high IL-18Rα expression on effector T cells is associated with increased disease severity. We find that IL-18Rα expression on CD8 T cells is inversely associated with cytotoxicity-related genes, including granzyme A, granzyme B, perforin, Eomes, and KLRG-1. Our study demonstrates that IL-18Rα is associated with severe and fatal respiratory disease outcomes and proposes the use of IL-18Rα as a potential biomarker for severe respiratory viral disease.

Suggested Citation

  • Aira F. Cabug & Jeremy Chase Crawford & Hayley A. McQuilten & Isabelle J. H. Foo & Lilith F. Allen & Deborah Gebregzabher & Robert C. Mettelman & Tanya Novak & Janet Chou & Louise C. Rowntree & Ruth R, 2025. "High expression of interleukin-18 receptor alpha correlates with severe respiratory viral disease and defines T cells with reduced cytotoxic signatures," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65262-5
    DOI: 10.1038/s41467-025-65262-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-65262-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-65262-5?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65262-5. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.