Defining the phenotype of neutrophils following reverse migration in zebrafish

Zebrafish reverse‐migrated neutrophils retain the ability to migrate to secondary wounds and mount a robust antibacterial response. Stimulation of neutrophil reverse migration presents an attractive, alternative therapeutic pathway to driving inflammation resolution. However, little is known about whether the activity of wound‐experienced neutrophils is altered and whether encouraging dispersal of such neutrophils back into the body may have undesirable consequences. This study used a zebrafish tail transection inflammation model, in combination with a photoconvertible neutrophil transgenic line, to allow internally controlled, simultaneous comparison of reverse‐migrated neutrophils with naïve neutrophils in the presence and absence of secondary insult. Detailed microscopy revealed that reverse‐migrated neutrophils exhibited an activated morphology but responded normally to secondary insult and are able to mount an effective antimicrobial response to Staphylococcus aureus. These results support a model in which reverse‐migrated neutrophils exhibit no long‐term behavioral alterations and encourage the notion of enhanced reverse migration as a viable target for pharmaceutical manipulation.