Figure 1.

Modulators of TREM-1 Activation. Activation of TREM-1 is inhibited by multiple agents: (1) GF9 and sneaking ligand construct to TREM-1 inhibit the interaction of TREM-1 with its signaling partner DAP12. (2) LR12/nangibotide, LP17, and TREM-1/Fc fusion protein act as decoy receptors and compete for binding with naturally occurring activating ligands. (3) Together with M3 and N1, LP17 also binds to TREM-1 and competitively inhibits ligand binding. M3 competitively inhibits TREM-1 binding to and activation by extracellular cold inducible RNA binding protein, while N1 inhibits TREM-1 activation by PGLYRP1 and HSP70. (4) soluble TREM-1 is generated from proteolytic cleavage of membrane bound TREM-1 by matrix metalloproteinases. Circulating soluble TREM-1 competitively binds TREM-1’s ligands and prevents further activation. All inhibitors prevent the downstream signaling cascade that upregulates the translation of inflammatory cytokines and TREM-1 receptor. Image created with BioRender .