Disruption of Cxcr3 chemotactic signaling alters lysosomal function and renders macrophages more microbicidal.
Cell Rep
; 35(2): 109000, 2021 04 13.
Article
em En
| MEDLINE
| ID: mdl-33852860
ABSTRACT
Chemotaxis and lysosomal function are closely intertwined processes essential for the inflammatory response and clearance of intracellular bacteria. We used the zebrafish model to examine the link between chemotactic signaling and lysosome physiology in macrophages during mycobacterial infection and wound-induced inflammation in vivo. Macrophages from zebrafish larvae carrying a mutation in a chemokine receptor of the Cxcr3 family display upregulated expression of vesicle trafficking and lysosomal genes and possess enlarged lysosomes that enhance intracellular bacterial clearance. This increased microbicidal capacity is phenocopied by inhibiting the lysosomal transcription factor EC, while its overexpression counteracts the protective effect of chemokine receptor mutation. Tracking macrophage migration in zebrafish revealed that lysosomes of chemokine receptor mutants accumulate in the front half of cells, preventing macrophage polarization during chemotaxis and reaching sites of inflammation. Our work shows that chemotactic signaling affects the bactericidal properties and localization during chemotaxis, key aspects of the inflammatory response.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peixe-Zebra
/
Transdução de Sinais
/
Proteínas de Peixe-Zebra
/
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos
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Receptores CXCR3
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Lisossomos
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Macrófagos
/
Infecções por Mycobacterium
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Holanda