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

Kam, JY; Hortle, E; Krogman, E; Warner, SE; Wright, K; Luo, K; Cheng, T; Manuneedhi Cholan, P; Kikuchi, K; Triccas, JA; Britton, WJ; Johansen, MD; Kremer, L; Oehlers, SH

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

Kam, JY Hortle, E

Krogman, E Warner, SE Wright, K Luo, K Cheng, T Manuneedhi Cholan, P Kikuchi, K Triccas, JA Britton, WJ Johansen, MD Kremer, L Oehlers, SH

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Publisher:: Nature Research
Publication Type:: Journal Article
Citation:: Nature Communications, 2022, 13, (1), pp. 1-11
Issue Date:: 2022-02-17

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Field	Value	Language
dc.contributor.author	Kam, JY
dc.contributor.author	Hortle, E https://orcid.org/0000-0001-9633-5638
dc.contributor.author	Krogman, E
dc.contributor.author	Warner, SE
dc.contributor.author	Wright, K
dc.contributor.author	Luo, K
dc.contributor.author	Cheng, T
dc.contributor.author	Manuneedhi Cholan, P
dc.contributor.author	Kikuchi, K
dc.contributor.author	Triccas, JA
dc.contributor.author	Britton, WJ
dc.contributor.author	Johansen, MD
dc.contributor.author	Kremer, L
dc.contributor.author	Oehlers, SH
dc.date.accessioned	2022-12-14T02:17:23Z
dc.date.available	2022-02-03
dc.date.available	2022-12-14T02:17:23Z
dc.date.issued	2022-02-17
dc.identifier.citation	Nature Communications, 2022, 13, (1), pp. 1-11
dc.identifier.issn	2041-1723
dc.identifier.issn	2041-1723
dc.identifier.uri	http://hdl.handle.net/10453/164392
dc.description.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.
dc.format	Electronic
dc.language	eng
dc.publisher	Nature Research
dc.relation.ispartof	Nature Communications
dc.relation.isbasedon	10.1038/s41467-022-28638-5
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.mesh	Animals
dc.subject.mesh	Animals, Genetically Modified
dc.subject.mesh	Bacterial Proteins
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Gene Knockdown Techniques
dc.subject.mesh	Granuloma
dc.subject.mesh	Host-Pathogen Interactions
dc.subject.mesh	Humans
dc.subject.mesh	Immunity, Innate
dc.subject.mesh	Lymphocyte Activation
dc.subject.mesh	Mycobacterium abscessus
dc.subject.mesh	Mycobacterium Infections, Nontuberculous
dc.subject.mesh	Persistent Infection
dc.subject.mesh	Signal Transduction
dc.subject.mesh	T-Lymphocytes, Regulatory
dc.subject.mesh	Tumor Necrosis Factor-alpha
dc.subject.mesh	Zebrafish
dc.subject.mesh	Zebrafish Proteins
dc.subject.mesh	Animals
dc.subject.mesh	Animals, Genetically Modified
dc.subject.mesh	Bacterial Proteins
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Gene Knockdown Techniques
dc.subject.mesh	Granuloma
dc.subject.mesh	Host-Pathogen Interactions
dc.subject.mesh	Humans
dc.subject.mesh	Immunity, Innate
dc.subject.mesh	Lymphocyte Activation
dc.subject.mesh	Mycobacterium Infections, Nontuberculous
dc.subject.mesh	Mycobacterium abscessus
dc.subject.mesh	Persistent Infection
dc.subject.mesh	Signal Transduction
dc.subject.mesh	T-Lymphocytes, Regulatory
dc.subject.mesh	Tumor Necrosis Factor-alpha
dc.subject.mesh	Zebrafish
dc.subject.mesh	Zebrafish Proteins
dc.subject.mesh	Animals
dc.subject.mesh	Animals, Genetically Modified
dc.subject.mesh	Zebrafish
dc.subject.mesh	Humans
dc.subject.mesh	Granuloma
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Tumor Necrosis Factor-alpha
dc.subject.mesh	Bacterial Proteins
dc.subject.mesh	Zebrafish Proteins
dc.subject.mesh	Lymphocyte Activation
dc.subject.mesh	Signal Transduction
dc.subject.mesh	T-Lymphocytes, Regulatory
dc.subject.mesh	Host-Pathogen Interactions
dc.subject.mesh	Immunity, Innate
dc.subject.mesh	Gene Knockdown Techniques
dc.subject.mesh	Mycobacterium Infections, Nontuberculous
dc.subject.mesh	Mycobacterium abscessus
dc.subject.mesh	Persistent Infection
dc.title	Rough and smooth variants of Mycobacterium abscessus are differentially controlled by host immunity during chronic infection of adult zebrafish.
dc.type	Journal Article
utslib.citation.volume	13
utslib.location.activity	England
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CFI - Centre for Inflammation
utslib.copyright.status	open_access	*
pubs.consider-herdc	false
dc.date.updated	2022-12-14T02:16:41Z
pubs.issue	1
pubs.publication-status	Published
pubs.volume	13
utslib.citation.issue	1

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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/164392