CD18 acts as an immune recognition molecule to induce the expressions of immune effectors through the Syk-ERK signaling pathway in oyster Crassostrea gigas.

Integrin β2 subunit (CD18) also known as the β subunit of complement receptor 3 (CR3) participates in the innate immunity through regulating multiple immune processes. In the present study, a CD18 molecule containing a signal peptide, an INB domain, a VWA domain, an EGF2 domain, an integrin B tail domain, a transmembrane domain and an integrin B cyt domain was identified from Crassostrea gigas. Its mRNA expressions in hemocytes increased significantly after Vibrio splendidus stimulation. CgCD18 proteins were mainly distributed in granulocytes of hemocytes. rCgCD18-VWA had the activities to bind various PAMPs and microbes. CgCD18 interacted with CgSyk and the blockage of CgCD18 with its antibody led to the decrease of CgH3K4 trimethylation, CgH3K9 acetylation, CgERK, and phosphorylated-CgERK. In anti-CgCD18-treated oysters, the mRNA expressions of CgIL17-1, CgIL17-2, CgIL17-3 and CgDefh2 decreased significantly in hemocytes. In addition, gill swelling, cilium shedding, vacuolization and gill flap enlargement were also significantly reduced. These results indicated that CgCD18 functioned as an immune recognition molecule to recognize various PAMPs and bacteria and then interacted with CgSyk to activate CgERK to induce CgH3K4 trimethylation and CgH3K9 acetylation, which eventually regulated the mRNA expressions of CgIL17-1, CgIL17-2, CgIL17-3, and CgDefh2.