Active nuclear transcriptome analysis reveals inflammasome-dependent mechanism for early neutrophil response to Mycobacterium marinum.
Sci Rep
; 7(1): 6505, 2017 07 26.
Article
em En
| MEDLINE
| ID: mdl-28747644
ABSTRACT
The mechanisms governing neutrophil response to Mycobacterium tuberculosis remain poorly understood. In this study we utilise biotagging, a novel genome-wide profiling approach based on cell type-specific in vivo biotinylation in zebrafish to analyse the initial response of neutrophils to Mycobacterium marinum, a close genetic relative of M. tuberculosis used to model tuberculosis. Differential expression analysis following nuclear RNA-seq of neutrophil active transcriptomes reveals a significant upregulation in both damage-sensing and effector components of the inflammasome, including caspase b, NLRC3 ortholog (wu fb15h11) and il1ß. Crispr/Cas9-mediated knockout of caspase b, which acts by proteolytic processing of il1ß, results in increased bacterial burden and less infiltration of macrophages to sites of mycobacterial infection, thus impairing granuloma development. We also show that a number of immediate early response genes (IEGs) are responsible for orchestrating the initial neutrophil response to mycobacterial infection. Further perturbation of the IEGs exposes egr3 as a key transcriptional regulator controlling il1ß transcription.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Mycobacterium marinum
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Perfilação da Expressão Gênica
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Inflamassomos
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Imunidade Inata
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Infecções por Mycobacterium não Tuberculosas
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Neutrófilos
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article