Towards a new model of trained immunity: Exposure to bacteria and β-glucan protects larval zebrafish against subsequent infections.

Once thought to be a feature exclusive to lymphocyte-driven adaptive immunity, immune memory has also been shown to operate as part of the innate immune system following infection to provide an elevated host response to subsequent pathogenic challenge. This evolutionarily conserved process, termed 'trained immunity', enables cells of the innate immune system to 'remember' previous pathogen encounters and mount stronger responses to the same, or different, pathogens after returning to a non-activated state. Here we show that challenging larval zebrafish, that exclusively rely on innate immunity, with live or heat-killed Salmonella typhimurium provides protection to subsequent infection with either Salmonella typhimurium or Streptococcus iniae, that lasts for at least 12 days. We also show that larvae injected with β-glucan, the well-known trigger of trained immunity, demonstrate enhanced survival to similar live bacterial infections, a phenotype supported by increased cxcl8 expression and neutrophil recruitment to the infection site. These results support the conservation of a trained immunity-like phenotype in larval zebrafish and provide a foundation to exploit the experimental attributes of larval zebrafish to further understand this form of immunological memory.