Arachidonic acid reverses microplastic-induced macrophage dysfunction in teleost fish.

Microplastic pollution poses a significant threat to aquaculture by compromising fish immunity, particularly macrophage function. This study investigated the impact of polystyrene microplastics (PS) on Nile tilapia (Oreochromis niloticus) macrophages and explored metabolic interventions to reverse PS-induced damage. PS exposure increased tilapia susceptibility to Streptococcus agalactiae infection, reducing fish survival. PS accumulated in head kidney macrophages, impairing phagocytosis, altering cytokine expression, elevating oxidative stress and malondialdehyde levels, and suppressing T-cell proliferation. Transcriptomics revealed PS dysregulated lysosomal pathways, reducing lysosomal membrane permeability and bacterial killing capacity. Metabolomic screening identified arachidonic acid (AA) as the most significantly suppressed metabolite in PS-exposed macrophages. Exogenous AA administration restored macrophage function including phagocytosis, cytokine expression, oxidative stress, enhanced lysosomal integrity, improved bactericidal activity, and increased survival during S. agalactiae challenge in PS-exposed fish. AA also reversed PS-induced transcriptional dysregulation of lysosomal genes. These results demonstrate that AA rectifies PS-induced macrophage dysfunction and lysosomal impairment, supporting its potential as a dietary supplement to mitigate microplastic immunotoxicity in aquaculture.