TLR4 and infection: Escudero-Pérez et al. (2014) demonstrated that shed GP but not secreted sGP activates dendritic cells and macrophages, resulting in a substantial upregulation of several cytokines in a TLR4-dependent manner. Iampietro et al. (2018) later observed that cell supernatant containing shed GP was sufficient to induce monocyte differentiation, an effect requiring functional TLR4, and ultimately resulting in increased infection and cell death. Recently, Scherm et al. (2022) demonstrated that cleavage by TACE protease is required for activation of TLR4/MD-2 by EBOV GP.