β-Glucan training induces stimulus-dependent immune and metabolic modulation in head kidney leukocytes that persists for several days in Atlantic salmon (Salmo salar L.)

Summary

The innate immune system of fish has conventionally been considered incapable of immunological memory but is now being recognised as exhibiting memory-like features known as trained immunity. This study investigated the induction of trained immunity in Atlantic salmon (Salmo salar L.) by training head kidney-derived leukocytes using β-glucan, followed by a resting phase and secondary stimulation with β-glucan (homologous) or lipopolysaccharide (LPS, heterologous). The cellular responses, metabolite production, and gene expression related to innate immunity, metabolism, and epigenetic markers were assessed. The effects of initial β-glucan training persisted after a 5-day resting period, during which upregulation occurred in the expression of key innate immune and metabolic genes. Upon secondary stimulation, leukocytes exhibited stimulus-dependent transcriptional responses with increased expression of several pro-inflammatory and metabolic genes, particularly in the heterologous LPS-exposed group. Attenuation of specific inflammatory cytokine responses occurred in trained cells upon LPS stimulation, but metabolic gene expression patterns indicated regulation toward enhancing glycolytic activity and mitochondrial oxidative metabolism. Trained cells also displayed significantly increased phagocytic activity, especially after heterologous exposure. Only minor or moderate changes occurred in other cellular outputs (reactive oxygen species, nitric oxide, lactate, and fumarate). Epigenetic markers showed limited expression changes. The experimental evidence indicates a phenotype similar to trained immunity in salmon leukocytes, characterised by transcriptional and functional alterations following β-glucan training; however, responses vary upon secondary exposure to a heterologous stimulus. This study provides new insight into trained immunity in Atlantic salmon by demonstrating the transcriptional and cellular response of leukocytes to develop stimulus-dependent immune and metabolic regulations.

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DOI : doi.org/10.3389/fimmu.2026.181...
NVA : hdl.handle.net/11250/5514480