SARM1 (Sterile Alpha and TIR Motif-Containing Protein 1), Fig. 2

SARM1 involves in host defense systems.(a) TIR-1, a SARM1 ortholog, acts through P38 MAPK cascades to trigger immune response after pathogen infection in C. elegans. (b) Human SARM1 inhibits both MYD88- and TRIF-dependent TLR3/4 signaling. TLR3 ligands, double-strand RNA or poly(I:C), activates TLR3 signaling through TRIF and the downstream factors such as TBK1, TRAF6, and PIPK1 to induce cytokine expression or apoptosis. LPS induces TLR4 signaling to trigger proinflammatory and anti-inflammatory cytokine expression via MYD88 and TRIF in plasma membrane or endosome, respectively. SARM1 inhibits both MYD88- and TRIF-dependent signaling