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