Guardians of the Lung: The Multifaceted Roles of Macrophages in Cancer and Infectious Disease

The lung as an organ that is fully exposed to the external environment for extended periods, comes into contact with numerous inhaled microorganisms. Lung macrophages are crucial for maintaining lung immunity and operate primarily through signaling pathways such as toll-like receptor 4 and nuclear factor-κB pathways. These macrophages constitute a diverse population with significant plasticity, exhibiting different phenotypes and functions on the basis of their origin, tissue residence, and environmental factors. During lung homeostasis, they are involved in the clearance of inhaled particles, cellular remnants, and even participate in metabolic processes. In disease states, lung macrophages transition from the inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. These distinct phenotypes have varying transcriptional profiles and serve different functions, from combating pathogens to repairing inflammation-induced damage. However, macrophages can also exacerbate lung injury during prolonged inflammation or exposure to antigens. In this review, we delve into the diverse roles of pulmonary macrophages the realms in homeostasis, pneumonia, tuberculosis, and lung tumors.