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 Str...
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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2007-09-01
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Series: | PLoS Pathogens |
Online Access: | http://europepmc.org/articles/PMC1971117?pdf=render |
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author | Jose Yuste Marina Botto Stephen E Bottoms Jeremy S Brown |
author_facet | Jose Yuste Marina Botto Stephen E Bottoms Jeremy S Brown |
author_sort | Jose Yuste |
collection | DOAJ |
description | 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. |
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issn | 1553-7366 1553-7374 |
language | English |
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spelling | doaj.art-f93de9d292c4461abacca73393dcf03b2022-12-21T19:26:16ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742007-09-01391208121910.1371/journal.ppat.0030120Serum amyloid P aids complement-mediated immunity to Streptococcus pneumoniae.Jose YusteMarina BottoStephen E BottomsJeremy S BrownThe 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.http://europepmc.org/articles/PMC1971117?pdf=render |
spellingShingle | Jose Yuste Marina Botto Stephen E Bottoms Jeremy S Brown Serum amyloid P aids complement-mediated immunity to Streptococcus pneumoniae. PLoS Pathogens |
title | Serum amyloid P aids complement-mediated immunity to Streptococcus pneumoniae. |
title_full | Serum amyloid P aids complement-mediated immunity to Streptococcus pneumoniae. |
title_fullStr | Serum amyloid P aids complement-mediated immunity to Streptococcus pneumoniae. |
title_full_unstemmed | Serum amyloid P aids complement-mediated immunity to Streptococcus pneumoniae. |
title_short | Serum amyloid P aids complement-mediated immunity to Streptococcus pneumoniae. |
title_sort | serum amyloid p aids complement mediated immunity to streptococcus pneumoniae |
url | http://europepmc.org/articles/PMC1971117?pdf=render |
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