Infection induced inflammation impairs wound healing through IL-1b signaling

Wound healing is impaired by infection; however, how microbe-induced inflammation modulates tissue repair remains unclear. We took advantage of the optical transparency of zebrafish and a genetically tractable microbe, Listeria monocytogenes, to probe the role of infection and inflammation in wound healing. We found a critical window of microbial clearance necessary to limit persistent inflammation and enable efficient wound repair. Infection with bacteria engineered to activate the inflammasome, Lm-Pyro, induced persistent inflammation and impaired healing despite low bacterial burden. In contrast, infection with an anti-inflammatory, apoptosis inducing strain, Lm-Apo, had similar infectious burden but was associated with rapid wound repair. Inflammatory infections induced il-1b expression and blocking IL-1R signaling partially rescued wound healing in the presence of persistent infection. Taken together, our findings suggest that the dynamics of microbe-induced tissue inflammation impacts repair in complex tissue damage independent of bacterial load, with a critical early window for efficient tissue repair. RNA-seq gene expression analysis of caudal fins of 4 dpf zebrafish after wounding and infection (n = 9: 3 replicates from each of 3 treatments)