Bulk RNA-seq of macrophages isolated from Salmonella Typhimurium infected zebrafish embryos

Bacterial infection involves a complex interaction between the pathogen
and host where the outcome of infection is not solely determined by
pathogen eradication. To identify small molecules that promote host
survival by altering the host-pathogen dynamic, we conducted
an in vivo chemical screen using zebrafish embryos and found that
treatment with 3-hydroxy-kynurenine protects from lethal gram-negative
bacterial infection. 3-hydroxy-kynurenine, a metabolite produced through
host tryptophan metabolism, has no direct antibacterial activity but
enhances host survival by restricting bacterial expansion in macrophages
by targeting kainate-sensitive glutamate receptors. These findings reveal
new mechanisms by which tryptophan metabolism and kainate-sensitive
glutamate receptors function and interact to modulate immunity, with
significant implications for the coordination between the immune and
nervous systems in pathological conditions.