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

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 Cg CLec-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 Cg CLec-HTM could bind LPS and various bacteria. After binding to its ligands, Cg CLec-HTM was associated with the Src homology 2 (SH2) domain of spleen tyrosine kinase ( Cg Syk) by the hemITAM in its cytoplasmic tail to promote ERK ( Cg ERK) phosphorylation. The activated Cg ERK could interact with Cg Rel to induce Cg Rel nuclear translocation. The Cg Rel in the nucleus eventually induced the transcription of Cg IL-17s and Cg TNF. The results demonstrated tha Cg CLec-HTM with a broad binding spectrum of bacteria could be associated with Cg Syk to transfer immune signals into the intracellular ERK-Rel pathway to induce Cg IL-17 and Cg TNF production.