Serum amyloid P aids complement-mediated immunity to Streptococcus pneumoniae.
The physiological functions of the acute phase protein serum amyloid P (SAP) component are not well defined, although they are likely to be important, as no natural state of SAP deficiency has been reported. We have investigated the role of SAP for innate immunity to the important human pathogen Streptococcus pneumoniae. Using flow cytometry assays, we show that SAP binds to S. pneumoniae, increases classical pathway-dependent deposition of complement on the bacteria, and improves the efficiency of phagocytosis. As a consequence, in mouse models of infection, mice genetically engineered to be SAP-deficient had an impaired early inflammatory response to S. pneumoniae pneumonia and were unable to control bacterial replication, leading to the rapid development of fatal infection. Complement deposition, phagocytosis, and control of S. pneumoniae pneumonia were all improved by complementation with human SAP. These results demonstrate a novel and physiologically significant role for SAP for complement-mediated immunity against an important bacterial pathogen, and provide further evidence for the importance of the classical complement pathway for innate immunity.
Yuste
Jose
J
Centre for Respiratory Research, Department of Medicine, Royal Free and University College Medical School, Rayne Institute, London, United Kingdom.
Botto
Marina
M
Bottoms
Stephen E
SE
Brown
Jeremy S
JS
D000818:Animals; D003167:Complement Activation / Q000502:physiology; D003179:Complement C3b / Q000502:physiology; D003165:Complement System Proteins / Q000502:physiology*; D004195:Disease Models, Animal; D007113:Immunity, Innate / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011008:Pneumococcal Infections / Q000276:immunology; D000683:Serum Amyloid P-Component / Q000235:genetics / Q000502:physiology*; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000472:pathogenicity
D000683:Serum Amyloid P-Component; D003179:Complement C3b; D003165:Complement System Proteins