(i) Early viral illness is characterized by the induction of IFN-α/β/λ and ISG expression to control viral replication and promote cell death and subsequent phagocytosis by CCL5-protected macrophages. (ii) Late viral illness includes lung DC migration to regional lymph nodes for MHC class I–dependent generation of CD8⁺ T cells and MHC class II–dependent generation of CD4⁺ Th2 cells and consequent B cell (and, in turn, plasma cell) production of antiviral antibodies (including IgE). (iii) Acute postviral disease is marked by IFN-α/β– and CD49⁺ polymorphonuclear (PMN) cell–dependent upregulation of FcεRI expression on resident lung DCs. In turn, FcεRI activation by viral antigen and antiviral IgE leads to the production of CCL28 and the recruitment of CCR10-expressing IL-13–producing Th2 cells to the lung. (iv) For chronic postviral disease, virus-activated APCs orchestrate CD1d-dependent glycolipid antigen presentation and consequent activation of iNKT cells. These iNKT cells then interact directly with lung macrophages via IL-13–IL-13R and invariant Vα14 TCR–CD1d interactions. These signals lead to increased expression of IL-13R and production of IL-13 that drives a positive feedback loop to amplify IL-13 production and activation of M2 macrophages, marked by chitinase 1 and arachidonate 15-LOX expression. In this immune axis, the airway epithelial cells may also release cytokines (e.g., IL-25, TSLP, and IL-33) that contribute to immune cell activation and chronic inflammatory disease in the form of asthma and COPD. Modified with permission from the American Journal of Respiratory Cell and Molecular Biology (140).