An arginase 2 promoter transgenic illuminates immune cell polarisation in zebrafish.

Abstract

The innate immune response to inflammation and infections are complex and represent major challenges for developing much needed new treatments for chronic inflammatory diseases and drug resistant infections. To be ultimately successful, the immune response must be balanced to allow pathogen clearance without excess tissue damage, processes controlled by pro- and anti-inflammatory signals. The roles of anti-inflammatory signalling in raising an appropriate immune response are underappreciated, representing overlooked potential drugs targets. This is especially true in neutrophils, a difficult cell type to study ex vivo due to a short lifespan, dogmatically seen as being highly pro-inflammatory. Here, we have generated and describe the first zebrafish transgenic line that labels expression of an anti-inflammatory gene (TgBAC(arg2:eGFP)sh571) and show that a subpopulation of neutrophils upregulate arginase early after immune challenge with injury and infection. At wound healing stages, arg2:GFP is expressed in subsets of neutrophils and macrophages, potentially representing anti-inflammatory, polarised immune cell populations. Our findings identify nuanced responses to immune challenge in vivo, responses that represent new opportunities for therapeutic interventions during inflammation and infection.