Mechanism by which pathogenic infection causes cell necroptosis

The mechanism by which pathogenic infection causes cell necroptosis. Pathogens trigger the necroptosis signaling pathway by activating multiple death receptors on the cell surface. The binding of TNF-α to TNFR triggers three different signaling responses: NF-κB activation, apoptosis or necroptosis. Respiratory syncytial virus (RSV), Mycoplasma hyopneumoniae and Mycobacterium tuberculosis (MTB) can induce cells to secrete TNF-α, thereby inducing the formation of RIPK1-RIPK3-MLKL necrosomes in cells and triggering necroptosis. MTB also prevents NF-κB activation by inhibiting RIPK1 ubiquitination. Death ligands, including FasL and TRAIL, trigger necroptosis by inducing necrosome formation by binding to the corresponding death receptors. SARS-CoV-2 activates IFNR by secreting IFN-γ and triggers necrosome formation through JAK-STAT1 to induce cell necroptosis. Streptococcus pneumoniae releases the pore-forming toxin pneumolysin (Ply) to induce cell damage and ion dysregulation, thereby triggering the formation of necrosomes in a death receptor-independent manner. Lipopolysaccharide (LPS) and double-stranded RNA (dsRNA) activate necroptosis through TRIF-mediated necrosome complex formation. SSL10 secreted by Staphylococcus aureus (SA) binds to TNFR and induces cell necroptosis by activating the RIPK1-RIPK3-MLKL and RIPK3-CaMKII mitochondrial permeability transition pore pathways. The Z-RNA produced by intracellular replication of Influenza Avirus (IAV) binds to ZBP1, leading to RIPK1-independent necroptosis through the ZBP1-RIPK3 complex

Publication

Necroptosis in Pneumonia: Therapeutic Strategies and Future Perspectives (2024) Xiuzhen Mei, et al. Viruses. 2024 Jan;16(1). Figure: F1. Homo sapiens

Disease mentions