Patrolling Alveolar Macrophages Conceal Bacteria from the Immune System to Maintain Homeostasis

During respiration, humans breathe in more than 10,000 liters of non-sterile air daily, allowing some pathogens access to alveoli. Interestingly, alveoli outnumber alveolar macrophages (AMs), which favors alveoli devoid of AMs. If AMs, like most tissue macrophages, are sessile, then this numerical advantage would be exploited by pathogens unless neutrophils from the blood stream intervened. However, this would translate to omnipresent persistent inflammation. Developing in vivo real-time intravital imaging of alveoli revealed AMs crawling in and between alveoli using the pores of Kohn. Importantly, these macrophages sensed, chemotaxed, and, with high efficiency, phagocytosed inhaled bacterial pathogens such as P. aeruginosa and S. aureus, cloaking the bacteria from neutrophils. Impairing AM chemotaxis toward bacteria induced superfluous neutrophil recruitment, leading to inappropriate inflammation and injury. In a disease context, influenza A virus infection impaired AM crawling via the type II interferon signaling pathway, and this greatly increased secondary bacterial co-infection. [Display omitted] •AMs patrol and clean the alveolar spaces•AMs have directed movement toward inhaled bacteria•AM migration is crucial for bacterial clearance•AM migration is impaired during viral infection Neupane et al. develop an intravital method to image alveolar macrophages in the lung in real time, overcoming the challenge presented by the air-liquid-air barrier of the alveoli. They use this in vivo approach to show that alveolar macrophages move between alveoli to provide efficient immune surveillance of the airway and phagocytosis of inhaled bacteria before they can induce harmful lung inflammation. Furthermore, they show that respiratory virus infections can interfere with alveolar macrophage surveillance, leading to bacterial superinfection.