Toll-like receptors (TLRs), known ligands, cellular localisation and effects of activation
| Receptor | Cellular localisation | Ligand | Agonist | Evidence from agonist treatment of virus infection | Refs |
| TLR2 (as heterodimer with TLR1 or TLR6) | Cell surface | Pam2Cys MALP-2 RV VP4 capsid SARS-CoV-2 envelope protein | Acylated lipopeptides Palmitic acid LP-1 Pam2C-SK4 PEG-diacylated lipopeptide Pam2Cys | Type-I IFN responses to vaccinia Protects from lethal influenza infection with no effect on adaptive immune responses Intranasal treatment limits influenza spread to lower airways Induces innate immune priming, enhances early type-III IFN responses and reduces viral load after RV infection Reduces upper respiratory tract viral shedding in SARS-CoV-2 challenge model | [32, 36–40] |
| TLR3 | Intra | dsRNA | Poly I:C PIKA Poly IC:LC | Protection from influenza yellow fever, Rift Valley fever, rabies Adjuvant protecting from HBV | [65, 71–76] |
| TLR4 | Cell surface | LPS RSV F EBOV G VSV G DENV NS1 | FimH MPLA | Protects from lethal influenza infection | [46–48] |
| TLR5 | Cell surface | Flagellin | Vaccine adjuvant for influenza Protects from CMV and influenza infection | [51–55] | |
| TLR7/TLR8 | Intra | ssRNA | R-848 Imiquimod Loxoribine | Vaccine adjuvant for influenza Antiviral approach for HBV/HCV | [93, 125–130] |
| TLR9 | Intra | Unmethylated DNA | CPG10101 CPG7909 | Protects from HCV infection Vaccine adjuvant for HIV | [114–116] |
| TLR10 | Cell surface | Unknown |
CMV: cytomegalovirus; DENV NS1: dengue virus non-structural protein 1; EBOV G: Ebola virus glycoprotein; FimH: fimbriae H protein; HBV: hepatitis B virus; HCV: hepatitis C virus; IFN: interferon; Intra: intracellular/endosomal; LPS: lipopolysaccharide; MALP: macrophage-activating lipopeptide; MPLA: monophosphoryl lipid A; PEG: pegylated; Poly I:C: polyinosinic:polycytidylic acid; Poly IC:LC: polyinosinic-polycytidylic acid stabilised with poly-L-lysine and carboxymethylcellulose; RSV F; respiratory syncytial virus via the fusion protein; RV: rhinovirus; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; VSV G: vesicular stomatitis virus glycoprotein.