Role of macrophage scavenger receptors in response to Listeria monocytogenes infection in mice.
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.
Ishiguro
T
T
Second Department of Pathology and Second Department of Internal Medicine, Niigata University School of Medicine, Niigata, Japan.
Naito
M
M
Yamamoto
T
T
Hasegawa
G
G
Gejyo
F
F
Mitsuyama
M
M
Suzuki
H
H
Kodama
T
T
D000818:Animals; D005838:Genotype; D006099:Granuloma / Q000235:genetics / Q000473:pathology; D007728:Kupffer Cells / Q000166:cytology / Q000502:physiology; D008089:Listeria monocytogenes; D008088:Listeriosis / Q000235:genetics / Q000382:microbiology* / Q000401:mortality; D008099:Liver / Q000382:microbiology / Q000473:pathology / Q000648:ultrastructure; D008107:Liver Diseases / Q000235:genetics / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D010587:Phagocytosis / Q000235:genetics; D010588:Phagosomes / Q000382:microbiology; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D016019:Survival Analysis; D015996:Survival Rate; D013997:Time Factors
D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A