PUBLICATION
Rough and smooth variants of Mycobacterium abscessus are differentially controlled by host immunity during chronic infection of adult zebrafish
- Authors
- Kam, J.Y., Hortle, E., Krogman, E., Warner, S.E., Wright, K., Luo, K., Cheng, T., Manuneedhi Cholan, P., Kikuchi, K., Triccas, J.A., Britton, W.J., Johansen, M.D., Kremer, L., Oehlers, S.H.
- ID
- ZDB-PUB-220219-11
- Date
- 2022
- Source
- Nature communications 13: 952 (Journal)
- Registered Authors
- Hortle, Elinor, Luo, Kaiming, Oehlers, Stefan
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Bacterial Proteins/genetics
- Bacterial Proteins/metabolism
- Disease Models, Animal
- Gene Knockdown Techniques
- Granuloma/immunology*
- Granuloma/microbiology
- Granuloma/pathology
- Host-Pathogen Interactions/immunology
- Humans
- Immunity, Innate
- Lymphocyte Activation
- Mycobacterium Infections, Nontuberculous/immunology*
- Mycobacterium Infections, Nontuberculous/microbiology
- Mycobacterium Infections, Nontuberculous/pathology
- Mycobacterium abscessus/genetics
- Mycobacterium abscessus/immunology
- Mycobacterium abscessus/pathogenicity*
- Persistent Infection/immunology*
- Persistent Infection/microbiology
- Persistent Infection/pathology
- Signal Transduction/immunology
- T-Lymphocytes, Regulatory/immunology
- Tumor Necrosis Factor-alpha/metabolism
- Zebrafish
- Zebrafish Proteins/metabolism
- PubMed
- 35177649 Full text @ Nat. Commun.
Citation
Kam, J.Y., Hortle, E., Krogman, E., Warner, S.E., Wright, K., Luo, K., Cheng, T., Manuneedhi Cholan, P., Kikuchi, K., Triccas, J.A., Britton, W.J., Johansen, M.D., Kremer, L., Oehlers, S.H. (2022) Rough and smooth variants of Mycobacterium abscessus are differentially controlled by host immunity during chronic infection of adult zebrafish. Nature communications. 13:952.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping