NK-lysin is an effector
protein of cytotoxic T lymphocytes and natural killer cells. Mammalian
NK-lysin is known to possess antibacterial property and antitumor activity. Homologues of
NK-lysin have been identified in several teleost species, but the natural function of fish
NK-lysin remains essentially unknown. In this study, we identified a
NK-lysin, CsNKL1, from half-smooth tongue sole (Cynoglossus semilaevis) and analyzed its expression, genetic organization, and
biological effect on pathogen
infection. CsNKL1 is composed of 135 residues and shares 33.1-56.5% overall sequence identities with other teleost
NK-lysin. CsNKL1 possesses a
Saposin B domain and six conserved
cysteine residues that in mammals are known to form three intrachain
disulfide bonds essential to antimicrobial activity. The genomic sequence of the ORF region of CsNKL1 is 1240bp in length and, like human
NK-lysin, contains five exons and four introns. Expression of CsNKL1 occurred in multiple tissues and was upregulated by bacterial and
viral infection in a time dependent manner. When CsNKL1 was overexpressed in tongue sole, significant upregulation of
interleukin-1 and
chemokines was observed in spleen and head kidney. Following bacterial and
viral infection, the pathogen loads in the tissues of CsNKL1-overexpressing fish were significantly lower than those in control fish. These results indicate that CsNKL1 possesses the novel capacities of
immunomodulation and enhancing antimicrobial defense against pathogens of both bacterial and viral nature.