Tissue osmotic surveillance shapes susceptibility of zebrafish to wound infections

Wounds represent compromised tissues that are susceptible to opportunistic infections. Tissue factors predisposing to wound infection include edema, poor vascularity, tissue hypoxia, necrosis, and wound size. However, it is unclear whether factors external to the tissue play a role. Detection of osmolarity imbalances between internal and external environment has been shown to alter epithelial wound closure and immune cell recruitment at injury sites. However, it remains unclear whether these osmotic surveillance pathways affect susceptibility to pathogenic wound infections. Here, we use live imaging and disease monitoring in zebrafish larvae to understand susceptibility of wound infection towards Pseudomonas aeruginosa. We show that exposure of wounds to isotonic solution results in enhanced susceptibility and pathogen burden. Furthermore, we demonstrate that this higher propensity for infection depends on osmolarity-mediated changes in wound sealing and neutrophil recruitment during the early stages of the wound response. These findings inform the design of experimental wound infection models as well as the clinical management of wounds.