Figure 1.

Macrophage anti-microbial mechanisms. (1) Bacteria are recognized by macrophage pattern recognition receptors (PRRs) such as Toll-like receptors (TLR), which bind conserved microbe-associated molecular patterns (MAMPs). (2) MAMP/PRR interaction triggers signaling cascades (e.g., IRF3, MAPKs, NF-κB) leading to macrophage responses, including formation of the phagocytic cup. (3) Internalized bacteria reside in phagosomes, from which nutrients and essential factors such as iron and magnesium are transported to the cytoplasm, restricting their supply to bacteria. Macrophages combine this starvation strategy with a poisoning mechanism involving phagosomal import of toxic amount of zinc and copper. (4) Phagosome maturation and fusion with lysosomes lead to acidification of the compartment lumen and activation of digestive enzymes such as proteases, which along with antimicrobial peptides (AMP), reactive oxygen and nitrogen species (ROS and RNS), lysozyme and lactoferrin contribute to bacterial killing. Macrophages can also undergo ETosis to release macrophage extracellular traps (MET) that immobilize and kill extracellular bacteria. (5) Additionally, infected macrophages secrete multiple cytokines to attract and activate other cells, which contribute to an effective immune response.