Table 2.

Platelet TLRs and their contribution to thrombosis and immunity

TLRs	Agonist	Interaction with cells	Result	Thrombosis	Platelet TLR- contribution to netosis	Organ netosis	Ref.
TLR2	Pam3CK4; oxPCCD36	neutrophils	Platelet-neutrophil HAGs through P-selectin; activation of GP2b/3a hyperreactivity and the prothrombotic state in the setting of hyperlipidemia	+	+ 136	?	35, 36
TLR4	LPS	neutrophils, monocytes	Platelets reduce the time of netosis in vivo; platelets aggregate in TLR4/MyD88- and cGMP/PKG-dependent pathway	+	+	+	33, 134
TLR3	pIC; pAU		Activation of NF-kappaB, PI3K-Akt and ERK1/2 pathways in platelets; at high agonist concentrations may potentiate platelet aggregation; liver netosis (pIC)	__	?	+	41, 42
TLR7	Loxoribine; R838	neutrophils	Modest increase of P-selectin and CD40 through AKT and p38-MAPK; no effect on platelet aggregation; liver netosis (R838)	__	?	+	40, 135
TLR9	CpG; Carboxy-alkylpyrrole protein adducts (CAPA)		Platelet clumping in presence of collagen (CpG); platelet activation, granule secretion, and aggregation in vitro and thrombosis in vivo via the TLR9/MyD88 pathway (CAPA)	__	?	?	38, 39

^*TLR3 may potentiate platelet aggregation at very high concentrations (50 µg/µl); Mitochondrial DNA can mediate netosis through TLR9.

Abbreviations: HAG- heterotypic aggregates; LPS-lipopolysaccharides; pIC- poly(I:C); pAU –poly(A:U);