The macrophage scavenger receptor A is host-protective in experimental meningococcal septicaemia

PLoS Pathog. 2009 Feb;5(2):e1000297. doi: 10.1371/journal.ppat.1000297. Epub 2009 Feb 13.


Macrophage Scavenger Receptor A (SR-A) is a major non-opsonic receptor for Neisseria meningitidis on mononuclear phagocytes in vitro, and the surface proteins NMB0278, NMB0667, and NMB1220 have been identified as ligands for SR-A. In this study we ascertain the in vivo role of SR-A in the recognition of N. meningitidis MC58 (serogroup B) in a murine model of meningococcal septicaemia. We infected wild-type and SR-A(-/-) animals intraperitoneally with N. meningitidis MC58 and monitored their health over a period of 50 hours. We also determined the levels of bacteraemia in the blood and spleen, and measured levels of the pro-inflammatory cytokine interleukin-6 (IL-6). The health of SR-A(-/-) animals deteriorated more rapidly, and they showed a 33% reduction in survival compared to wild-type animals. SR-A(-/-) animals consistently exhibited higher levels of bacteraemia and increased levels of IL-6, compared to wild-type animals. Subsequently, we constructed a bacterial mutant (MC58-278-1220) lacking two of the SR-A ligands, NMB0278 and NMB1220. Mutation of NMB0667 proved to be lethal. When mice were infected with the mutant bacteria MC58-278-1220, no significant differences could be observed in the health, survival, bacteraemia, and cytokine production between wild-type and SR-A(-/-) animals. Overall, mutant bacteria appeared to cause less severe symptoms of septicaemia, and a competitive index assay showed that higher levels of wild-type bacteria were recovered when animals were infected with a 1ratio1 ratio of wild-type MC58 and mutant MC58-278-1220 bacteria. These data represent the first report of the protective role of SR-A, a macrophage-restricted, non-opsonic receptor, in meningococcal septicaemia in vivo, and the importance of the recognition of bacterial protein ligands, rather than lipopolysaccharide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteremia / immunology*
  • Bacteremia / microbiology
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Cloning, Molecular
  • Data Interpretation, Statistical
  • Disease Models, Animal
  • Female
  • Host-Pathogen Interactions / genetics*
  • Interleukin-6 / blood
  • Interleukin-6 / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Meningococcal Infections / immunology*
  • Meningococcal Infections / microbiology
  • Mice
  • Mice, Inbred BALB C
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Neisseria meningitidis, Serogroup B / genetics
  • Neisseria meningitidis, Serogroup B / growth & development
  • Neisseria meningitidis, Serogroup B / metabolism*
  • Scavenger Receptors, Class A / genetics*
  • Scavenger Receptors, Class A / physiology
  • Spleen / cytology
  • Spleen / pathology
  • Survival Analysis


  • Bacterial Proteins
  • Interleukin-6
  • Mutant Proteins
  • Scavenger Receptors, Class A