Tumor necrosis factor α2 (TNFα2) facilitates gut barrier breach by Aeromonas hydrophila and exacerbates liver injury in hybrid fish.

TNFα is a multifunctional cytokine that can modulate immune homeostasis and promote cellular regulation in mammals, but the crucial role of TNFα in fish gut remained unclear. The current study aimed to evaluate the immunoregulatory function of TNFα2 on gut barrier breach by A. hydrophila and systemic pathogenesis in gut and liver of WR (White crucian carp ♀ × red crucian carp ♂). WR-TNFα2 encoded 232 amino acid residues and showed a high-level of WR-TNFα2 expression in spleen. After A. hydrophila and lipopolysaccharide (LPS) stimulated, elevated levels of WR-TNFα2 expressions were detected in immune-related tissues and cultured fish cells, respectively. Gut perfusion with WR-TNFα2 alone could alter antioxidant status, increase extrinsic apoptosis as well as promote inflammatory response in midgut, causing severe injury of epithelial barrier. Moreover, WR-TNFα2-treated midgut exhibited a decline of mucosal protection against invasive A. hydrophila , which could elevate bacterial burden in tissues, aggravate tissue injury as well as attenuate immune activation. Our results suggested that WR-TNFα2 could exhibit a detrimental effect on gut barrier defense against A. hydrophila infection and dysregulate immune response in midgut and liver of hybrid crucian carp. • The predicted structure and expression patterns of TNFα2 were firstly reported in WR. • WR-TNFα2 altered antioxidant status and increased extrinsic apoptosis in midgut. • WR-TNFα2 facilitated bacterial infection by impairing gut barrier and then exacerbated liver lesion. [ABSTRACT FROM AUTHOR]