Macrophage NFATC2 mediates angiogenic signaling during mycobacterial infection.
Cell Rep
; 41(11): 111817, 2022 12 13.
Article
en En
| MEDLINE
| ID: mdl-36516756
ABSTRACT
During mycobacterial infections, pathogenic mycobacteria manipulate both host immune and stromal cells to establish and maintain a productive infection. In humans, non-human primates, and zebrafish models of infection, pathogenic mycobacteria produce and modify the specialized lipid trehalose 6,6'-dimycolate (TDM) in the bacterial cell envelope to drive host angiogenesis toward the site of forming granulomas, leading to enhanced bacterial growth. Here, we use the zebrafish-Mycobacterium marinum infection model to define the signaling basis of the host angiogenic response. Through intravital imaging and cell-restricted peptide-mediated inhibition, we identify macrophage-specific activation of NFAT signaling as essential to TDM-mediated angiogenesis in vivo. Exposure of cultured human cells to Mycobacterium tuberculosis results in robust induction of VEGFA, which is dependent on a signaling pathway downstream of host TDM detection and culminates in NFATC2 activation. As granuloma-associated angiogenesis is known to serve bacterial-beneficial roles, these findings identify potential host targets to improve tuberculosis disease outcomes.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Tuberculosis
/
Mycobacterium marinum
/
Mycobacterium tuberculosis
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Rep
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos