Macrophage NFATC2 mediates angiogenic signaling during mycobacterial infection

• DOI: 10.1016/j.celrep.2022.111817
• Publication Date: 2022-12-13T16:23:55Z
• Authors: W. Jared Brewer; Ana María Xet-Mull; Anne Yu; Mollie I. Sweeney; Eric M. Walton; David M. Tobin
• Keywords: NFAT; Lipoarabinomannan

Highlights•NFAT signaling induces VEGFA in macrophages downstream of a bacterial glycolipid•NFATC2 is required for angiogenesis induced by mycobacterial trehalose 6,6′-dimycolate•Macrophage-specific inhibition NFAT blocks during infection•In vivo, macrophage-specific reduces burdenSummaryDuring infections, pathogenic mycobacteria manipulate both host immune and stromal cells to establish maintain productive infection. In humans, non-human primates, zebrafish models infection, produce modify the specialized lipid 6,6′-dimycolate (TDM) cell envelope drive toward site forming granulomas, leading enhanced growth. Here, we use zebrafish-Mycobacterium marinum infection model define basis angiogenic response. Through intravital imaging cell-restricted peptide-mediated inhibition, identify activation as essential TDM-mediated vivo. Exposure cultured human Mycobacterium tuberculosis results robust induction VEGFA, which dependent on pathway TDM detection culminates NFATC2 activation. As granuloma-associated known serve bacterial-beneficial roles, these findings potential targets improve disease outcomes.Graphical abstract