Table 1.
TLRs, their cellular location, major ligands with their source, TLR SNPs and disease association.
| TLRs | TLR polymorphism (SNP and nucleic acid variant) | TLR polymorphism and disease association | TLR localization | Ligands | Origin of ligands |
|---|---|---|---|---|---|
| TLR1 | T1805G (I602S) R80T | 602S SNP in TLR1 is protective against Leprosy caused by Mycobacterium leprae [397] R80T is associated with increased risk of Aspergillosis [514,515] |
Plasma membrane | Triacyl lipopeptide Soluble factors |
Bacteria and mycobacteria |
| TLR2 | T597C R753Q, SNP-15607A/G of haplotype 2 of TLR2 | T597C SNP Protects against leprosy but predisposes towards tuberculosis infection [516,517] R753Q increases susceptibility to S. aureus infection [518], 15607A/G of haplotype 2 of TLR2 is associated with increased viral shedding and lesional rate in patients with genital herpes simplex virus (HSV) Type 2 infection [519] |
Plasma membrane | PGN, LTA, Lipoproteins or lipopeptides, lipoarabinomannan, A phenol-soluble modulin, Glycoinositolphosp-holipids, glycolipids, porins, zymosan, atypical LPS, Hsp70, EDN | Gram +ve bacteria, mycobacteria, S. epidermidis, Trypanosoma cruzi, Treponema maltophilum, Neisseria, Fungi, Leptospira interrogans, Porphyromonas gingivalis, host, host |
| TLR3 | rs1879026 (G/T), rs13126816, rs3775291, L412F TLR3 polymorphism, 299698T/G, 293248A/A, 299698T/T | rs1879026 (G/T) is linked to increased prevalence of hepatitis B virus infection [520], rs13126816 and rs3775291 are associated with protection against human herpes simplex virus type 2 (HSV-2) infections [521], L412F TLR3 polymorphism is associated with resistance against HIV infection in the Italian population [522], and same SNP in Japanese population is associated with protection against acute graft rejection in adult patients receiving liver transplantation for hepatitis C virus (HCV)-related cirrhosis [523], 299698T/G, 293248A/A, 299698T/T SNPs in the exon of TLR3 are Stevens-Johnson syndrome (SJS), mucocutaneous disease in Japanese patients [524] | Endolysosome | dsRNA | Viruses |
| TLR4 | A896G or D299G C1196T or T399I are non-synonymous SNPs and are linkage disequilibrium [525] | D299G TLR4 polymorphism is associated with increased incidence of gram negative bacteraemia and sepsis [528]. This SNP is also linked to Mediaterranean spotted fever caused by Rickettesia conorii [527]. Humans with T399I TLR4 polymorphism milder hyporesponsive phenotype to LPS [528]. Cosegregation of both D299G and T399I TLR4 SNPs more severe hyporesponsive enss to LPS and higher incidence of sepsis and severe form RSV infection [[529], [530], [531]] | Plasma membrane | LPS, Taxol, Fusion protein, Envelope proteins, HMG-B1, Hsp60, Hsp70, Hsp22, Hsp96, Type III repeat extra domain A of fibronectin, oligosaccharides of hyaluronic acids, polysaccharide fragments of heparin sulphate, fibrinogen, saturated fatty-acids and Fetuin-A | Gram negative bacteria, Plant, RSV, MMTV, Chlamydia pneumoniae, Chlamydia trachomatis, host |
| TLR5 | C1174T (R392) (replacement of sequence encoding Arg392 with a stop codon) Present in 10% of European population [532,533] |
People with this SNP are more prone to develop Legionella pneumophila infections or Legionnaires' disease (Legionellosis) [534] and recurrent cystitis [535]. | Plasma membrane | Flagellin | Bacteria |
| TLR6 | A1401G (a TLR6 promoter SNP) C744T | Associated with high risk of prostate cancer in patients homo or heterozygous for A1401G [394], People with TLR6 C744T exhibit protection against asthma [536] | Plasma membrane | Di-acyl lipopeptides, Zymosan | Mycoplasma |
| TLR7 | Intron I, c.IT-120G | c.1-120G TLR7 allele protects male patients to develop inflammation and fibrosis during chronic HCV-infection [537] | Endolysosome | ssRNA, loxoribine, bropirimine | Viruses, synthetic compounds |
| TLR8 | 129G | Male patients infected with chronic HCV infection exhibit less inflammation due to less IFN-α production [538] | Endolysosome | ssRNA | Viruses |
| TLR9 | G-1174A and A1635G | People with these two SNPs in TLR9 exhibit rapid progressor phenotype for HIV-1 infection [539,540] | Endolysosome | CpG oligodeoxyneucleotide (ODN), Hemozoin pigment | Bacteria and viruses (HSV), Malaria |
| TLR10 | ND | ND | Endolysosome | ND | ND |
| TLR11 | NA | NA | Endolysosome | Profilin-like protein | Toxoplasma gondii |
| TLR12 | NA | NA | Endolysosome | Profilin-like protein | Toxoplasma gondii |
| TLR13 | NA | NA | Endolysosome | 23s ribosomal RNA | Bacteria |