Macrophage

Macrophages ("big eaters") are found in every tissue. Many tissue-resident populations — microglia, Kupffer cells, alveolar macrophages and epidermal Langerhans cells — are seeded before birth from yolk-sac and fetal-liver progenitors and maintain themselves by local proliferation; others, including those of the gut and dermis and the macrophages that flood inflamed tissues, are continuously replenished by blood monocytes. They are large (≈ 20–50 µm) cells with an oval or indented nucleus and abundant cytoplasm rich in lysosomes, phagosomes and vacuoles, together forming the mononuclear phagocyte system (formerly "reticuloendothelial system").

Macrophages recognise microbes through pattern-recognition receptors (Toll-like receptors, mannose and scavenger receptors) and opsonins (IgG via Fcγ receptors; C3b via complement receptors), engulf them and kill them in phagolysosomes using reactive oxygen and nitrogen species and lysosomal enzymes. They clear apoptotic cells (efferocytosis), senescent red cells and debris; secrete cytokines (IL-1, IL-6, TNF-α, IL-12, CXCL8) that drive fever, the acute-phase response and recruitment of other leukocytes; and present antigen on MHC class II to effector CD4 T cells.

Their behaviour depends on signals from the environment, along a spectrum often simplified as M1 ("classically activated") — induced by IFN-γ (from Th1 and NK cells) and microbial products, highly microbicidal (inducible nitric oxide synthase) and pro-inflammatory — and M2 ("alternatively activated") — induced by IL-4 and IL-13, anti-inflammatory and involved in helminth defence, tissue repair (PDGF, TGF-β, VEGF) and fibrosis. Persistent antigen that cannot be cleared leads macrophages to form granulomas: aggregates of epithelioid macrophages and multinucleated giant cells surrounded by lymphocytes.