CgCLec-HTM–Mediated Signaling Pathway Regulates Lipopolysaccharide-Induced CgIL-17 and CgTNF Production in Oyster

Abstract The immune signaling pathway mediated by Dectin-1 is important in mammals to modulate the production of IL-17 and TNF-α. Recently, IL-17 and TNF have also been characterized in invertebrates to play crucial roles in antibacterial immune responses, although the immune recognition and regulation mechanisms to produce IL-17 and TNF are still not well investigated. In the current study, a novel C-type lectin receptor (named CgCLec-HTM) with a signal peptide, a carbohydrate recognition domain, a transmembrane domain, and a nonclassical ITAM (hemITAM) in the cytoplasmic tail was identified from oyster Crassostrea gigas. CgCLec-HTM could bind LPS and various bacteria. After binding to its ligands, CgCLec-HTM was associated with the Src homology 2 (SH2) domain of spleen tyrosine kinase (CgSyk) by the hemITAM in its cytoplasmic tail to promote ERK (CgERK) phosphorylation. The activated CgERK could interact with CgRel to induce CgRel nuclear translocation. The CgRel in the nucleus eventually induced the transcription of CgIL-17s and CgTNF. The results demonstrated that CgCLec-HTM with a broad binding spectrum of bacteria could be associated with CgSyk to transfer immune signals into the intracellular ERK–Rel pathway to induce CgIL-17 and CgTNF production.