Figure 1.

Shared responses in lung innate cells in response to respiratory virus infection and allergen exposure. Viral infection and/or allergen exposure of bronchial epithelial cells results in the secretion of the innate type-2 cytokines: thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, and IL-33. Dendritic cells (DCs), macrophages, and innate type 2 lymphoid cell (ILC2s) are among the first responders in the lung. Each of these cytokines increases activation of DCs, including increased expression of OX40L. OX40L expressing DCs drive Th2 differentiation in the lung mediastinal lymph nodes. These innate type-2 cytokines also promote differentiation of M2 alternatively activated macrophages (AAM), which secrete type-2 cytokines IL-4, IL-13, and IL-10 and orchestrate type-2 inflammation and tissue repair in the lung. M2 macrophage cytokine/chemokine production contributes to enhanced type-2 biased inflammation and airway remodeling. IL-5 and IL-13 production from ILC2s promotes eosinophil influx and responses in DCs and macrophages that further enhance type-2 inflammation, Th2 differentiation, and airway hyperresponsiveness (AHR). Each of these responses is enhanced in neonates upon exposure to respiratory viruses, setting the stage for enhanced type-2 inflammation upon exposure to allergens.