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

Dis Model Mech. 2023 Jun 1;16(6):dmm049966. doi: 10.1242/dmm.049966. Epub 2023 May 3.

Abstract

Innate immune responses to inflammation and infection 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 drug targets. This is especially true in neutrophils, a difficult cell type to study ex vivo owing to a short lifespan, dogmatically seen as being highly pro-inflammatory. Here, we have generated and describe the first zebrafish transgenic line [TgBAC(arg2:eGFP)sh571] that labels expression of the anti-inflammatory gene arginase 2 (arg2) and show that a subpopulation of neutrophils upregulate arginase soon 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.

Keywords: Anti-inflammatory; Infection; Inflammation; Macrophage; Neutrophil; Zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Anti-Inflammatory Agents / metabolism
  • Arginase* / genetics
  • Arginase* / metabolism
  • Inflammation
  • Neutrophils
  • Zebrafish* / metabolism

Substances

  • Arginase
  • Anti-Inflammatory Agents