Modulation of Tumor Necrosis Factor by Microbial Pathogens
Figure 2
Different Strategies for Inhibiting TNF by Pathogens
Pathogens have evolved diverse strategies to target almost every step of TNF biology. Virus-encoded proteins inhibit TNF-mediated responses by directly binding to TNF with secreted soluble decoy TNFR (vTNFRs) and vTNFBPs, downregulating the cellular death receptors, interacting with the TNFR-associated factors, blocking caspase activation, and regulating the apoptotic checkpoint function of mitochondria. Viruses also regulate the pathways leading to TNF-mediated activation of NF-κB. Bacteria and other pathogens can express proteins that regulate TNF-mediated responses by activating or inhibiting NF-κB at different levels of signaling that range from the death receptor to nuclear localization of NF-κB.