Toll-like receptor 9 and 21 have different ligand recognition profiles and cooperatively mediate activity of CpG-oligodeoxynucleotides in zebrafish

Zebrafish Toll-like receptor (TLR) 9 (zebTLR9) and TLR21 (zebTLR21) have distinct CpG-oligodeoxynucleotide (CpG-ODN) sequence recognition profiles. The recognition profile of zebTLR9 is more like that of the TLR9s from mouse and rabbit, whereas the recognition profile of zebTLR21 is more similar to that of human TLR9 and TLR9s from domestic animals. These two zebTLRs are requlated by UNC93B1 and cooperatively mediate the immunologic and antimicrobial responses induced by CpG-ODN in zebrafish. Our findings address the molecular basis of CpG-ODN activities in zebrafish and provide information for the rational design of CpG-ODN for use as an antimicrobial agent in fishes.