TLR9 is essential for macrophage production of TNFα and IL-6 in response to CpG DNA and IFNγ produced by CD4+ T cells in response to CpG DNA and mycobacteria.15, 27 The observation that ammonia-induced TLR9 activation induces systemic inflammation and brain edema is well supported by recently published studies that show TLR9 induces inflammation in acetaminophen-induced ALF and nonalcoholic steatohepatitis.16, 20. This evidence concerns the gene CD4 and metabolic dysfunction-associated steatohepatitis.