Besides TLR4, other receptors potentially involved in PD1 and 2B4 upregulation could be TLR2 and TLR9, as bacterial DNA as a TLR9 ligand was elevated in blood of HFD fed mice (Miura et al., 2010) and free fatty acids as well as denatured host DNA could activate these two receptors in the course of NASH development (Senn, 2006; Watanabe et al., 2007). This evidence concerns the gene TLR4 and metabolic dysfunction-associated steatohepatitis.