Fish-specific TLR18 in Nile tilapia (Oreochromis niloticus) recruits MyD88 and TRIF to induce expression of effectors in NF-κB and IFN pathways in melanomacrophages

Trung NB 1 , Nan FH 2 , Lee MC 3 , Loh JY 4 , Gong HY 5 , Lu MW 5 Show all authors , Hang HT 5 , Lin YL 5 , Lee PT 6

Affiliations 

  • 1 Department of Aquaculture, National Taiwan Ocean University, Keelung, Taiwan, ROC; College of Aquaculture and Fisheries, Can Tho University, Viet Nam
  • 2 Department of Aquaculture, National Taiwan Ocean University, Keelung, Taiwan, ROC; Center of Excellence for Ocean Engineering, National Taiwan Ocean University, 11, Keelung City, 20224, Taiwan
  • 3 Department of Aquaculture, National Taiwan Ocean University, Keelung, Taiwan, ROC; Center of Excellence for Ocean Engineering, National Taiwan Ocean University, 11, Keelung City, 20224, Taiwan; Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung City, 20224, Taiwan
  • 4 Faculty of Applied Sciences, UCSI University, Cheras, Kuala Lumpur, Malaysia
  • 5 Department of Aquaculture, National Taiwan Ocean University, Keelung, Taiwan, ROC
  • 6 Department of Aquaculture, National Taiwan Ocean University, Keelung, Taiwan, ROC. Electronic address: leepotsang@email.ntou.edu.tw
Fish Shellfish Immunol, 2021 Dec;119:587-601.
PMID: 34743023 DOI: 10.1016/j.fsi.2021.11.001

Abstract

Toll-like receptors (TLRs) are evolutionarily conserved proteins of pattern recognition receptors (PRRs) and play a crucial role in innate immune systems recognition of conserved pathogen-related molecular samples (PAMPs). We identified and characterized TLR18 from Nile tilapia (Oreochromis niloticus), OnTLR18, to elucidate its role in tissue expression patterns, modulation of gene expression after microbial challenge and TLR ligands, subcellular localization in fish and human cells, and the possible effectors TLR18 induces in a melanomacrophage-like cell line (tilapia head kidney (THK) cells). OnTLR18 expression was detected in all tissues examined, with the highest levels in the intestine and the lowest in the liver. OnTLR18 transcript was up-regulated in immune-related organs after bacterial and polyinosinic-polycytidylic acid (poly I:C) challenges and in the THK cells after lipopolysaccharide (LPS) stimulation. In transfected THK and human embryonic kidney (HEK) 293 cells, OnTLR18 localizes in the intracellular compartment. OnMyD88 and OnTRIF, but not OnTIRAP, were co-immunoprecipitated with OnTLR18, suggesting that the former two molecules are recruited by OnTLR18 as adaptors. The constitutively active form of OnTLR18 induced the production of pro-inflammatory cytokines, type I interferon (IFN), and antimicrobial peptides such as tumor necrosis factor α, interferon (IFN) d2.13, tilapia piscidin (TP)2, TP3, TP4, and hepcidin in THK cells. Our results suggest that OnTLR18 plays an important role in innate immunity through initiating nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and IFN signaling pathways via OnMyD88 and OnTRIF and induces the production of various effectors in melanomacrophages.

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