Table 2.

Summary of pathogenic, endogenous and synthetic ligands for pattern recognition receptors.

TLR Ligands
Receptor	Organism	Ligand Class	Molecules	References
TLR2 (TLR1/TLR2; TLR2/TLR6)	M/H	Pathogenic	Lipoptroteins; Triacetylated lipopeptides; human β-defensin 3 (BD-3); Glycosylphosphatidylinositol (GPI); Zymosan; Peptidoglycan; LPS; Lipoproteine/-peptide; Glycolipide; MALP-2; Diacetylierte Lipopeptide; LTA; Zymosan	[244,245,246,247] [248,249,250,251,252,253,254,255,256,257,258]
		Endogenous	Endoplasmin; Hsp60; Hsp70; Human cardiac myosin; Urate crystals; Hyaluronan	[259,260,261,262,263,264]
		Synthetic	FSL-1, synthetic lipopeptides & lipoprotein analogs, triacetylated lipopeptides e.g., Pam2CSK4, Pam3CSK4, or synthetic beta-defensin 3, MALP2	[244,245,258], [265,266,267,268]
TLR3	M/H	Pathogenic	dsRNA	[269,270,271]
		Endogenous	mRNA	[270]
		Synthetic	poly(I:C); poly(A:U)	[258,272,273,274]
TLR4 (MD-2; CD14)	M/H	Pathogenic	Lipopolysaccharid (LPS; Gram-); Lipoteichoic acid (LTA; Gram+)	[256,275,276]
		Endogenous	β-defensin 2; Fibronectin; Fibrinogen; Hyaluronan; Surfactant protein A; Urate crystals; OxPAPC; Hsp72; Hsp70; Hsp60; HMGB1; Endoplasmin	[262,264,277,278,279,280,281,282], [259,260,283,284]
		Synthetic	Glycan-based agonists; Monophosphoryl Lipid A (MPL); pyrimido[5,4-b]-indoles; LPS	[268,285,286,287]
TLR5	M/H	Pathogenic	Flagellin	[248,288]
		Endogenous	Unknown
		Synthetic	Flagellin	[289,290]
TLR7	M/H	Pathogenic	ssRNA	[291,292,293]
		Endogenous	RNA; siRNA	[294,295]
		Synthetic	Imiquimod (R837); Resiquimod (R848); Gardiquimod; Loxoribine	[268,274,296,297,298,299,300,301]
TLR8	M/H	Pathogenic	TLR7 antagonist (mouse); ssRNA (human)	[292,299,302,303]
		Endogenous	Human cardiac myosin; siRNA	[295,304]
		Synthetic	Imiquimod (R837); Resiquimod (R848); Gardiquimod; TL8-506	[268,274,296,297,298,299,300,301]
TLR9	M/H	Pathogenic	Unmethylated CpG DNA; dsDNA	[258,269,305,306]
		Endogenous	DNA; HMGB1	[307,308,309]
		Synthetic	Diverse synthetic CpG-oligonucleotides (CpG-ODNs)	[268,274,310,311,312]
TLR10	H	Pathogenic	Non functional in mice (viral insertion); TLR2 antagonist; HIV-1 gp41	[120,313,314]
		Endogenous	Unknown
		Synthetic	Unknown
TLR11	M	Pathogenic	Profilin	[95,120,315]
		Endogenous	Unknown
		Synthetic	Unknown
TLR12	M	Pathogenic	Profilin	[120,315,316]
		Endogenous	Unknown
		Synthetic	Unknown
TLR13	M	Pathogenic	Bacterial 23S rRNA	[120,123]
		Endogenous	Unknown
		Synthetic	Unknown
CD180	M/H	Pathogenic	Unknown
		Endogenous	Negative regulator of TLR7 & TLR9	[317]
		Synthetic	Unknown
STING ligands	Organism	Ligand Class	Molecules	Literature
Receptor
STING	M/H	Pathogenic	Bacterial cyclic di-nucleotides and cGAMP; viral DNA	[111,206,210,211]
		Endogenous	Self-DNA e.g., dead cells, DNA leaking into the cytosol following stress or tumor DNA; tumor cGAMP	[220,225,227,228]
		Synthetic	Cyclic dinucleotides e.g., 2′-3′-cGAMP; c-di-AMP; di-amidobenzimidazole	[301,318]
RLR ligands	Organism	Ligand Class	Molecules	Literature
Receptor
RIG-I	M/H	Pathogenic	Paramyxoviridae, Rhabdoviridae & Orthomyxoviridae; short dsRNA; dsDNA in cooperation with RNA Polymerase III; 5′-phosphorylated ssRNAs	[110,155,158,160,319]
		Endogenous	Endogeneous RNAs e.g., LINE1	[320,321]
		Synthetic	poly(dA:dT); tri-phosphorylated 5′ stem-loop RNAs	[158,322,323]
MDA-5	M/H	Pathogenic	Picornaviridae; long dsRNA; ssRNA; dsDNA; NAB2; rb-dsRNA	[110,155,160,322,324]
		Endogenous	Endogeneous RNAs e.g., mitochondrial RNA and retroelement transcripts	[320,325,326,327]
		Synthetic	poly(I:C)	[160,322]

M = murine, H = human.