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

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

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1038/s41467-022-28638-5
Journal or Publication Title: Nature Communications
Volume: 13
Number: 1
Date: 2022
Divisions: Tuberculosis
Depositing User: General Admin
Identification Number: 10.1038/s41467-022-28638-5
ISSN: 2041-1723
Date Deposited: 17 Mar 2022 00:43
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.

Creators:
Creators
Email
Kam, Julia Y.
UNSPECIFIED
Hortle, Elinor
UNSPECIFIED
Krogman, Elizabeth
UNSPECIFIED
Warner, Sherridan E.
UNSPECIFIED
Wright, Kathryn
UNSPECIFIED
Luo, Kaiming
UNSPECIFIED
Cheng, Tina
UNSPECIFIED
Manuneedhi Cholan, Pradeep
UNSPECIFIED
Kikuchi, Kazu
UNSPECIFIED
Triccas, James A.
UNSPECIFIED
Britton, Warwick J.
UNSPECIFIED
Johansen, Matt D.
UNSPECIFIED
Kremer, Laurent
UNSPECIFIED
Oehlers, Stefan H.
UNSPECIFIED
Last Modified: 17 Mar 2022 00:43
URI: https://eprints.centenary.org.au/id/eprint/1202

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