Figure 2.

Roles of alveolar macrophages in resistance and resilience during pneumonia. As sentinel cells, alveolar macrophages sound the initial alarm and are essential to the rapid activation of other cells, the recruitment of neutrophils, and the killing of bacteria. In addition, alveolar macrophages are effectors of antibacterial resistance, capable of killing ingested bacteria, especially when undergoing apoptosis. The apoptosis of other cells in the lung stimulates alveolar macrophage efferocytosis, which eliminates dying leukocytes, prevents their release of danger signals in the lungs, and switches macrophage phenotypes to producing anti-inflammatory and proresolving signals. Select subsets of alveolar macrophages become nonmotile and adhere to the epithelium via gap junctions, through which these macrophages transmit Ca²⁺ waves that dampen inflammatory signaling. However, when nonapoptotic pathways of cell death are triggered by microbial virulence factors, alveolar macrophages become poor bacteria killers and release powerful proinflammatory signals that can exacerbate lung injury.