Macrophage

Macrophages are large phagocytic cells of the immune system that derive from monocytes and reside in tissues throughout the body. They originate from hematopoietic stem cells in the bone marrow; monocytes circulate in the blood and differentiate into macrophages when they migrate into tissues. Distinct populations exist, including alveolar macrophages in the lung, Kupffer cells in the liver, microglia in the brain, and osteoclasts in bone.

Macrophages perform several key functions. They phagocytose and digest microbes, dead cells, and debris in phagolysosomes and kill ingested microbes using reactive oxygen and nitrogen species. They clear aging or damaged cells through efferocytosis and recycle nutrients. They also present antigens to T cells via MHC class II molecules, linking innate and adaptive immunity, and secrete a broad range of cytokines and chemokines that regulate inflammation, antimicrobial defense, and tissue repair.

Macrophage activity is supported by a wide array of receptors, including scavenger receptors, Fc receptors, complement receptors, and pattern recognition receptors such as Toll-like receptors. These receptors detect microbial components and danger signals, guiding activation, phagocytosis, and cytokine production. Macrophages exhibit considerable plasticity, often described as a spectrum between pro-inflammatory (M1) and anti-inflammatory/wound-healing (M2) phenotypes in response to signals such as IFN-γ and LPS for M1, or IL-4 and IL-13 for M2; in reality, states are more nuanced.

In health, macrophages contribute to host defense, tissue homeostasis, and repair. In disease, they can participate in protective responses or contribute to pathology, as in chronic inflammatory diseases, atherosclerosis, and cancer, where tumor-associated macrophages may promote tumor progression or suppress immune responses.