A healthy and NOX2-deficient alveolus. A healthy alveolus populated with sentinel resident CD11b^low AMs that can capture cellular debris to maintain homeostasis (left). NOX2 deficiency results in (1) phagocytic CD11b^low AMs that can capture cellular debris but also release production of proinflammatory cytokines and chemokines, followed by the emergence of (2) a CD11b^high AM population, derived from either resident AMs or recruited monocytes, and by overall lung inflammation in mice and humans, characterized by (3) an increase in proinflammatory cytokines and (4) recruitment and activation of neutrophils (right). IFN-α, interferon-α; IL-18, interleukin-18; TNF-α, tumor necrosis factor-α.