CgIL17-5, an ancient inflammatory cytokine in Crassostrea gigas exhibiting the heterogeneity functions compared with vertebrate interleukin17 molecules

• The CgIL17-5 transcripts were increased post twice Vibrio splendidus challenge.
• CgIL17-5 could induce the secretion of IL6 in HuVEC cells.
• CgIL17-5 could activate transcription factors such as NF-κB and CREB in vitro.
• CgIL17-5 exhibited PAMPs binding activity and antibacterial activity.

Interleukin 17 (IL17) is a proinflammatory cytokine that plays an important role in immune response. Recently, five novel IL17 homologs have been identified by screening and analyzing the genome of pacific oyster Crassostrea gigas. In the present study, the functions of CgIL17-5 were investigated by examining the distribution of its mRNA and protein, ligands binding and modulation in immune response. The mRNA expression levels of CgIL17-5 in hemocytes of oysters post twice challenges of Vibrio splendidus were all significantly up-regulated (P < 0.01), while the secondary pathogen infection attenuated the expression level of CgIL17-5 mRNA compared with the primary challenge. CgIL17-5 was found to be located on oyster hemocyte membranes through fluorescence confocal assay. The luciferase reporter assays showed that CgIL17-5 could activate the transfactors NF-κB, CREB and ATF-1, and involve in their signal pathways in HEK293T cells. Meanwhile, CgIL17-5 could augment the IL6 synthesis in HuVEC cells, playing the similar roles as human IL17 in inflammatory response. Additionally, the recombinant CgIL17-5 (rCgIL17-5) could directly bind peptidoglycan (PGN), lipopolysaccharide (LPS), poly (I:C) and β-1,3-glucan, with the highest affinity to PGN, and significantly inhibit the growth of Micrococcus luteus and Escherichia coli. All the results collectively suggested that CgIL17-5, as an ancient inflammatory cytokine, could not only activate signal transduction for the release of other cytokines, but also mediate the clearance of extracellular bacteria in oysters.