Location, function, and ontogeny of pulmonary macrophages during the steady state.

The lung is continuously exposed to potentially hazardous environmental challenges in the form of inert material and microbes. Pulmonary macrophages are critical in maintaining a low inflammatory context in the lung to facilitate optimal gas exchange. During infection, however, they mediate the immediate response to invading microorganisms in coordination with epithelial cells and other tissue-resident immune cells including dendritic cells, innate lymphocytes and memory T cells, and pulmonary interstitial macrophages. The balance between pulmonary Mø inhibition and activation is regulated by a complex set of receptors whose activation determines whether macrophages remain quiescent or undergo cellular activation. In addition, pulmonary macrophages perform tissue-specific functions such as surfactant catabolism necessary to prevent alveolar proteinosis and interstitial lung disease. This review summarizes current knowledge on different pulmonary macrophage types with an emphasis on their location, function, and available experimental models to manipulate them. Finally, we review recent developments on the dynamic ontogeny of pulmonary macrophages and how it may affect age-related diseases.