Mediators of Inflammation

Review Article

TIRAP, TRAM, and Toll-Like Receptors: The Untold Story

Table 1

Cellular compartments for TLR signaling effector recruitment.


TLR effector	Related pathway	TLR	PI lipids	Cellular compartments	Cell types	References

TIRAP	NF-κB	TLR2, TLR4	PI(4,5)P₂	Plasma membrane	Human monocytes, macrophages	[28, 78]
		TLR4, TLR9	PI(3,5)P₂	Lysosome	BMDMs	[62, 67]
	IFN I (via IRF7)	TLR4	PI3P, PI5P	Early endosome	MEFs, macrophages	[17, 27]
TRAM	IFN I (via TRIF)				Macrophages	[22]
TBK1		TLR3, TLR4	PI5P		MEFs, GMDCs	[71]
IRF3

Abbreviations: BMDMs: bone marrow-derived macrophages; GMDCs: genetically modified dendritic cells; IFN I: type I interferons; IRF3: interferon regulatory factor 3; IRF7: interferon regulatory factor 7; MEFs: mouse embryonic fibroblasts; NF-κB: nuclear factor-κB; PI: phosphatidylinositol; PI3P: phosphatidylinositol-3-phosphate; PI5P: phosphatidylinositol-5-phosphate; PI(3,5)P₂: phosphatidylinositol-3,5-biphosphate; PI(4,5)P₂: phosphatidylinositol-4,5-biphosphate; TBK1: TRAF-associated NF-κB activator-binding kinase 1; TIRAP: Toll/interleukin-1 receptor domain-containing adaptor protein; TLR: Toll-like receptor; TRAM: TRIF-related adaptor molecule; TRIF: TIR domain-containing adaptor-inducing interferon-β.