The stereotypic inflammatory response provoked by toll-like receptor activation has prompted speculation that endogenous activators of toll-like receptors might participate in autoimmune diseases.  TLRs have been suspected of binding to host molecules including fibrinogen (involved in blood clotting), heat shock proteins (HSPs), HMGB1, extracellular matrix components and self DNA (it is normally degraded by nucleases, but under inflammatory and autoimmune conditions it can form a complex with endogenous proteins, become resistant to these nucleases and gain access to endosomal TLRs as TLR7 or TLR9). These endogenous ligands are usually produced as a result of non-physiological cell death.