Role of scavenger receptor in the processing of bacterial antigens

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Type I and type II macrophage scavenger receptors (MSR-A I/II) recognize a variety of polyanions including bacterial cell wall products such as lipopolysaccharide. suggesting a role for MSR-A I/II in immunity against bacterial infection.In the first study, we used mice lacking the MSR-A to elucidate the role of MSR-A in endotoxin shock. Peritoneal macrophages from MSR-A-deficient (MSR-A-/-) mice bound less remarkably to LPS than those from wild type (MSR-A+/+) mice. Clearance of LPS in serum was retarded in MSR-A-/- mice after intraperitoneal administration of LPS, suggesting that MSR-A function as a receptor for LPS.LPS-induced expressions of IL-1 βwere lower in MSR-A-/- than MSR-A+/+ mice.Administration of large doses of LPS resulted in a higher mortality of MSR-A+/+ than of MSR-A-/- mice, and pretreatment with an IL-1 receptor antagonist reduced the mortality.In the second study, we clarified that MSR-A-/- mice were more susceptible to infection with listeriolysin-O (LLO)-producing listeria monocytogenes. After infection, Kupffer cells in wild type (MSR-A+/+) mice phagocytized larger numbers of Listeria than those in MSR-A-/- mice. Listeria monocytogenes replicated at higher levels in the liver of MSR-A-/- mice compared with MSR-A+/+ mice, and macrophages from MSR-A-/- mice showed impaired ability to kill listeria in vitro. SR-A I/II function as a receptor for L.monocytogenes. Electron microscopic observation on the intracytoplasmic behavior of bacteria revealed that SR-A I/II plays a crucial role in host defense against listerial infection not only by functioning as a receptor but also by mediating listericidal mechanisms through the regulation of LLO-dependent listerial escape from the macrophages.