Fig. 3.

Type-I IFNs synthesis happens through multiple cascades (discussed in main text) and is indispensable to induce immunity and its expression operates in various cell types, including DC and macrophages. Chiefly pDC plays a central role in the earliest production of IFN-α/β. In response to viral infection, TLR7 and TLR9 gets stimulated and trigger a robust MyD88-dependent and IRF-7 mediated type-I IFN signalling, involving production of large amounts of IFN-α and IFN-β (IFN-α/β). Stimulation of cytosolic radars RIG-1 and MDA-5, engages the mitochondrial antiviral-signalling MAVS adaptor protein, which results in IRF3-mediated signalling. cDCs and macrophages although not responsible for the IFN-α/β production during the early phase (24 hrs) of infection but generate protective immunity during the effector phase. The IFNs secreted works in an autocrine and paracrine manner via binding to its cognate receptor and initiating JAK-STAT signalling for IFN-γ and cytokines production including IL-6 and TNFα. Virus infected cells show increased inflammation due to activation of the multiprotein inflammasome complex, NLRP3. It activates caspase-I, which triggers the release of pro-inflammatory cytokines IL-1β and IL-18, involved in pyroptosis.