{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe class A scavenger receptor MARCO is widely expressed on tissue‐resident macrophages and several dendritic cell subpopulations, where it plays a central role in innate immune defense. MARCO binds and internalizes a diverse array of unopsonized pathogens, environmental particles, and endogenous ligands, thereby facilitating bacterial clearance, particle sequestration, and the resolution of sterile inflammation. In various in vivo models—including pneumococcal pneumonia, mycobacterial infection, and particulate exposure—MARCO‐expressing macrophages were shown to be critical for both efficient ligand uptake and for modulating the onset and magnitude of inflammatory responses. This binding and clearance function helps restrict further tissue injury and modulates host immune activation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in direct pathogen clearance, MARCO modulates inflammatory signaling by cooperating with key pattern‐recognition receptors such as toll‐like receptors (TLRs) and CD14. This cooperation enhances the activation of downstream signaling pathways—such as NF‑κB and MAPKs—that trigger production of pro‐inflammatory cytokines and chemokines in responses to bacterial glycolipids and other microbial ligands. Moreover, MARCO influences antigen–presentation dynamics by impacting the actin cytoskeletal architecture during dendritic cell maturation, thereby shaping subsequent adaptive immune responses. These immunomodulatory roles underscore the receptor’s importance in orchestrating both immediate innate defenses and longer‐term immune polarization."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond these functions, MARCO also participates in the modulation of viral infections, neuroinflammatory processes, and metabolic homeostasis. By enhancing viral entry in some settings (for example, by aiding adenovirus or herpes simplex virus uptake) or by facilitating the clearance of viral particles via cooperation with intracellular sensors, MARCO ultimately influences both the severity and outcome of infections. Its regulatory roles extend to tissue remodeling and macrophage polarization in metabolic diseases, as well as in conditions such as osteolysis and post‑influenza secondary bacterial pneumonia. Collectively, these observations not only reveal the multifaceted functions of MARCO in host defense but also highlight its promise as a therapeutic target to modulate inflammation and infection."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "31"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Annika Brännström, Marko Sankala, Karl Tryggvason, et al. 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