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

Kam, Julia Y. and Hortle, Elinor and Krogman, Elizabeth and Warner, Sherridan E. and Wright, Kathryn and Luo, Kaiming and Cheng, Tina and Manuneedhi Cholan, Pradeep and Kikuchi, Kazu and Triccas, James A. and Britton, Warwick J. and Johansen, Matt D. and Kremer, Laurent and Oehlers, Stefan H. (2022) Rough and smooth variants of Mycobacterium abscessus are differentially controlled by host immunity during chronic infection of adult zebrafish. Nature Communications, 13 (1). ISSN 2041-1723

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Link to published document: http://doi.org/10.1038/s41467-022-28638-5

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.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 14 Apr 2022 03:23
Last Modified: 14 Apr 2022 06:03
URI: http://eprints.victorchang.edu.au/id/eprint/1203

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