The involvement of TNF-α and TNF-β as proinflammatory cytokines in lymphocyte-mediated adaptive immunity of Nile tilapia by initiating apoptosis.

Tumor necrosis factors (TNFs) are pleiotropic cytokines with important functions in homeostasis and disease pathogenesis. Recent advances have shown that TNFs are also involved in the regulation of adaptive immune responses. However, the knowledge about how TNF participates in and regulates adaptive immune response in early vertebrates is still limited. In present study, we identified two isoforms of TNF, TNF-α and TNF-β, from Nile tilapia Oreochromis niloticus (On-TNF-α and β). After analyzing the sequence characteristics, we investigated their regulatory roles in adaptive immune response of this fish species. On-TNF-α and β are evolutionarily conserved compare with their homologs from other vertebrates. Both TNFs were distributed in a wide range of tissues in O. niloticus, and with relative higher expression level in gill. After the animals were infected by Streptococcus agalactiae, mRNA levels of On-TNF-α and TNF-β in spleen lymphocytes were significantly upregulated during the primary response stage of adaptive immunity. Meanwhile, both TNF proteins in spleen lymphocytes were also dramatically elevated during the adaptive immune stage after bacterial infection. These results indicate the potential participation of On-TNF-α and TNF-β in adaptive immune response of Nile tilapia. Furthermore, On-TNF-α and β transcripts were obviously augmented, once spleen lymphocytes were activated by T cell-specific mitogen PHA. More importantly, both recombinant On-TNF-α and β could induce the apoptosis of head-kidney leukocytes of Nile tilapia. And On-TNF-β but not On-TNF-α promoted the apoptosis by activating caspase-8 in the target cells. Altogether, our study revealed that TNF-α and TNF-β participated in the lymphocyte-mediated adaptive immune response of Nile tilapia by initiating the apoptosis, and thus shed novel perspective for the regulatory mechanism of adaptive immunity in teleost.