Anarginase 2promoter transgenic illuminates anti-inflammatory signalling in zebrafish

AbstractThe innate immune response to inflammatory stimuli must be finely balanced to produce an appropriate pro-inflammatory response while allowing a subsequent return to homeostasis. In recent years,in vivotransgenic zebrafish models have shed light on the temporal regulation of the pro-inflammatory innate response to immune challenges. However, until now, there have been no zebrafish transgenic models of anti-inflammatory signalling. We compared existing expression data of arginase genes in zebrafish neutrophils and macrophages, strong candidates for an anti-inflammatory marker, and identified thatarginase 2is the most highly expressed Arginase in zebrafish immune cells. We developed anarginase 2(arg2) bacterial artificial chromosome (BAC) transgenic line,TgBAC(arg2:eGFP)sh571, driving GFP expression under the control of thearg2promoter. We show that, under resting conditions,arg2:GFPis expressed in ionocytes, matching thein situhybridisation pattern. Upon immune challenge by injury, bacterial and fungal insults,arg2:GFPis predominantly expressed in neutrophils at early timepoints post-insult. Later in infections,arg2:GFPis expressed in cells associated with foci of infection (including neutrophils and macrophages), alongside liver expression. Our data indicate thatarginase 2is predominantly expressed in neutrophils after immune challenge and suggest that anti-inflammatory signals coincide with pro-inflammatory signals during early wound and infection responses.