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Rough and smooth variants of Mycobacterium abscessus are differentially controlled by host immunity during chronic infection of adult zebrafish

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  • Julia Y. Kam

    (Tuberculosis Research Program at the Centenary Institute, The University of Sydney)

  • Elinor Hortle

    (Tuberculosis Research Program at the Centenary Institute, The University of Sydney
    The University of Sydney, Faculty of Medicine and Health & Marie Bashir Institute)

  • Elizabeth Krogman

    (Tuberculosis Research Program at the Centenary Institute, The University of Sydney)

  • Sherridan E. Warner

    (Tuberculosis Research Program at the Centenary Institute, The University of Sydney
    The University of Sydney, Faculty of Medicine and Health & Marie Bashir Institute)

  • Kathryn Wright

    (Tuberculosis Research Program at the Centenary Institute, The University of Sydney)

  • Kaiming Luo

    (Tuberculosis Research Program at the Centenary Institute, The University of Sydney)

  • Tina Cheng

    (Tuberculosis Research Program at the Centenary Institute, The University of Sydney)

  • Pradeep Manuneedhi Cholan

    (Tuberculosis Research Program at the Centenary Institute, The University of Sydney)

  • Kazu Kikuchi

    (Victor Chang Cardiac Research Institute
    University of New South Wales)

  • James A. Triccas

    (The University of Sydney, Faculty of Medicine and Health & Marie Bashir Institute)

  • Warwick J. Britton

    (Tuberculosis Research Program at the Centenary Institute, The University of Sydney
    Royal Prince Alfred Hospital)

  • Matt D. Johansen

    (Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier)

  • Laurent Kremer

    (Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier
    INSERM, IRIM)

  • Stefan H. Oehlers

    (Tuberculosis Research Program at the Centenary Institute, The University of Sydney
    The University of Sydney, Faculty of Medicine and Health & Marie Bashir Institute
    Agency for Science, Technology and Research (A*STAR))

Abstract

Prevalence of Mycobacterium abscessus infections is increasing in patients with respiratory comorbidities. After initial colonisation, M. abscessus smooth colony (S) variants can undergo an irreversible genetic switch into highly inflammatory, rough colony (R) variants, often associated with a decline in pulmonary function. Here, we use an adult zebrafish model of chronic infection with R and S variants to study M. abscessus pathogenesis in the context of fully functioning host immunity. We show that infection with an R variant causes an inflammatory immune response that drives necrotic granuloma formation through host TNF signalling, mediated by the tnfa, tnfr1 and tnfr2 gene products. T cell-dependent immunity is stronger against the R variant early in infection, and regulatory T cells associate with R variant granulomas and limit bacterial growth. In comparison, an S variant proliferates to high burdens but appears to be controlled by TNF-dependent innate immunity early during infection, resulting in delayed granuloma formation. Thus, our work demonstrates the applicability of adult zebrafish to model persistent M. abscessus infection, and illustrates differences in the immunopathogenesis induced by R and S variants during granulomatous infection.

Suggested Citation

  • Julia Y. Kam & Elinor Hortle & Elizabeth Krogman & Sherridan E. Warner & Kathryn Wright & Kaiming Luo & Tina Cheng & Pradeep Manuneedhi Cholan & Kazu Kikuchi & James A. Triccas & Warwick J. Britton & , 2022. "Rough and smooth variants of Mycobacterium abscessus are differentially controlled by host immunity during chronic infection of adult zebrafish," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28638-5
    DOI: 10.1038/s41467-022-28638-5
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    References listed on IDEAS

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    1. Stefan H. Oehlers & Mark R. Cronan & Ninecia R. Scott & Monica I. Thomas & Kazuhide S. Okuda & Eric M. Walton & Rebecca W. Beerman & Philip S. Crosier & David M. Tobin, 2015. "Interception of host angiogenic signalling limits mycobacterial growth," Nature, Nature, vol. 517(7536), pages 612-615, January.
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