Proinflammatory CD16+CD14+CD206- alveolar macrophages expressing RAGE and NLRP3 were more frequent, and those expressing TXNIP less frequent, in patients with ARDS than in those without ARDS, supporting a novel proof-of-concept of RAGE–TXNIP–NLRP3-driven mechanisms of macrophage activation during acute lung injury. The gene discussed is TXNIP; the disease is acute respiratory distress syndrome.