PUBLICATION
Macrophage NFATC2 mediates angiogenic signaling during mycobacterial infection
- Authors
- Brewer, W.J., Xet-Mull, A.M., Yu, A., Sweeney, M.I., Walton, E.M., Tobin, D.M.
- ID
- ZDB-PUB-221216-15
- Date
- 2022
- Source
- Cell Reports 41: 111817111817 (Journal)
- Registered Authors
- Tobin, David
- Keywords
- CP: Immunology, CP: Microbiology, Mycobacterium marinum, Mycobacterium tuberculosis, NFAT, Vegfa, angiogenesis, macrophage, pathogenic mycobacteria, trehalose dimycolate, zebrafish
- MeSH Terms
-
- Animals
- Granuloma/pathology
- Humans
- Macrophages/metabolism
- Mycobacterium marinum*
- Mycobacterium tuberculosis*
- NFATC Transcription Factors/metabolism
- Signal Transduction
- Tuberculosis*
- Zebrafish/microbiology
- PubMed
- 36516756 Full text @ Cell Rep.
Citation
Brewer, W.J., Xet-Mull, A.M., Yu, A., Sweeney, M.I., Walton, E.M., Tobin, D.M. (2022) Macrophage NFATC2 mediates angiogenic signaling during mycobacterial infection. Cell Reports. 41:111817111817.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping