Fig. 8: Lipid peroxidation in infection.
From: Emerging mechanisms of lipid peroxidation in regulated cell death and its physiological implications
Toll-like receptor 4 (TLR4) has an important role in innate immunity. The oxygenated lipids can activate TLR4 to further induce the activation of adapter TICAM1 or MYD88. Next, the activated TLR4 induces type I IFN signaling and NF-κB pathways to promote lipid peroxidation-related inflammation. Besides, AGER recognizes multiple DAMPs (e.g. HMGB1), leading to the activation of inflammatory signaling pathways, including phosphatidylinositol 3-kinase (PI3K)-protein kinase B, protein kinase C (PKC), RAS-MAPK and JAK-STAT. In STING1 pathways, lipid peroxidation can damage mitochondrial and DNA, whereas the release of mtDNA, 8-OHG and damaged DNA activates the STING1-dependent inflammatory pathway via the DNA sensor CGAS. However, lipid peroxides (e.g., 4-HNE) can directly inhibit STING1 activity by the carbonylation of STING1.
