Role of macrophage scavenger receptors in response to Listeria monocytogenes infection in mice.

Abstract

Type I and type II macrophage scavenger receptors (SR-A I/II) recognize a variety of polyanions including bacterial cell-wall products such as lipopolysaccharide, suggesting a role for SR-A I/II in immunity against bacterial infection. SR-A I/II-deficient (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. The number and the diameter of hepatic granulomas were larger in MSR-A-/- mice than MSR-A+/+ mice. L. 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. However, macrophages from MSR-A+/+ and MSR-A-/- mice showed similar levels of listericidal activity against isogenic mutant L. monocytogenes with an inactivated LLO gene. The listerial phagocytic activities of MSR-A+/+ macrophages treated with an anti-SR-A I/II antibody (2F8) and MSR-A-/- macrophages were significantly impaired compared with untreated MSR-A+/+ macrophages, indicating that SR-A I/II function as a receptor for L. monocytogenes. Electron microscopy revealed that most L. monocytogenes had been eliminated from the lysosomes of MSR-A+/+ macrophages in vivo and in vitro. In contrast, L. monocytogenes rapidly lysed the phagosomal membrane and escaped to the cytosol in MSR-A-/- macrophages and in MSR-A+/+ macrophages treated with 2F8 before phagosome-lysosome fusion. These findings imply 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.

• Authors: T Ishiguro, M Naito, T Yamamoto, G Hasegawa, F Gejyo, M Mitsuyama, H Suzuki, T Kodama
• Journal: The American journal of pathology (Am J Pathol) Vol. 158 Issue 1 Pg. 179-88 (Jan 2001) ISSN: 0002-9440 [Print] United States
• PMID: 11141491 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Immunologic
• Receptors, Scavenger
• Scavenger Receptors, Class A

Topics

• Animals
• Genotype
• Granuloma (genetics, pathology)
• Kupffer Cells (cytology, physiology)
• Listeria monocytogenes
• Listeriosis (genetics, microbiology, mortality)
• Liver (microbiology, pathology, ultrastructure)
• Liver Diseases (genetics, pathology)
• Macrophages (cytology, physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Microscopy, Electron
• Phagocytosis (genetics)
• Phagosomes (microbiology)
• Receptors, Immunologic (genetics, physiology)
• Receptors, Scavenger
• Scavenger Receptors, Class A
• Survival Analysis
• Survival Rate
• Time Factors