The cell recognizes pathogens upon binding of the so-called PAMPs to PRRs. In addition, there is increasing evidence showing that these PRRs also sense endogenous danger signals, known as DAMPs that are released by necrotic cells. 107 The PRR group consists of Toll-like receptors (TLRs), NLRs, retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) and C-type lectin receptors. Depending on the cellular context, PRR triggering can induce different types of cell death. To date, TLR-mediated necrotic cell death has been described in cells triggered by TLR3, -4 and -9. Recognition of dsRNA or poly(I:C) (synthetic dsRNA analog) by TLR3 and lipopolysaccharide (LPS) by TLR4 triggers the recruitment of an adaptor called Toll-interleukin-1 receptor domain-containing adaptor inducing interferon-b, 108,109 which interacts with both RIPK1 and RIPK3 via its RHIM domain, 110 suggesting the possible involvement of RIPK1 and RIPK3 in TLR3-and TLR4-induced necrosis. Indeed, poly(I:C)-induced necroptotic cell death in the presence of interferon-b is inhibited in RIPK1-deficient cells 111 or when RIPK1 kinase activity is blocked. 24,34 Recently, it has been reported that poly(I:C) stimulation in a steatohepatitis disease model induces necrosis that is correlated with an increase in RIPK3 expression, indicating a possible role for RIPK3 in poly(I:C)induced regulated necrosis in vivo. 112 Triggering TLR4 by LPS prevents necrotic cell death of macrophages when either RIPK1 or RIPK3 is absent by RNA interference-mediated knockdown. 18,113 Together, these **data** suggest that TLR3 and TLR4 stimulation may induce RIPK1-and RIPK3dependent necroptosis (Figure 2b).