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

Am J Pathol. 2001 Jan;158(1):179-88. doi: 10.1016/S0002-9440(10)63956-9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


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