Serum amyloid P aids complement-mediated immunity to Streptococcus pneumoniae
| العنوان: | Serum amyloid P aids complement-mediated immunity to Streptococcus pneumoniae |
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| المؤلفون: | Stephen E Bottoms, Jeremy S. Brown, Jose Yuste, Marina Botto |
| المصدر: | PLoS Pathogens, Vol 3, Iss 9, Pp 1208-1219 (2007) PLoS Pathogens |
| بيانات النشر: | Public Library of Science (PLoS), 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Streptococcus Pneumoniae, lcsh:Immunologic diseases. Allergy, genetic structures, Immunology, Mice, Transgenic, Inflammation, Biology, medicine.disease_cause, Microbiology, Pneumococcal Infections, Mice, 03 medical and health sciences, Classical complement pathway, 0302 clinical medicine, Immunity, Virology, Streptococcus pneumoniae, Genetics, medicine, Animals, Respiratory Medicine, Complement Activation, Molecular Biology, lcsh:QH301-705.5, Serum amyloid P component, 030304 developmental biology, 0303 health sciences, Innate immune system, Pentraxin, Complement System Proteins, medicine.disease, Innate Immunity, Immunity, Innate, 3. Good health, Complement system, Mice, Inbred C57BL, Disease Models, Animal, Serum Amyloid P-Component, Pneumococcal infections, lcsh:Biology (General), Complement C3b, biology.protein, Parasitology, medicine.symptom, lcsh:RC581-607, Research Article, 030215 immunology |
| الوصف: | 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. Author Summary Serum amyloid P (SAP) is a protein that is found in high concentrations in the blood, the exact function(s) of which are not clear. However, no known natural state of SAP deficiency has been identified, which suggests that SAP does have a vital role in human health. SAP can bind to molecular patterns found on the surface of bacteria, and it has been proposed that this may mark bacteria for attack by the immune system. We have investigated whether SAP helps protect against an important bacterial pathogen, Streptococcus pneumoniae. We show that SAP binds to different strains of S. pneumoniae, and that this leads to activation of an important component of the immune response called the complement system. Complement is particularly important for defence against S. pneumoniae infections, and using animal models of infection, we demonstrate that loss of SAP makes mice more susceptible to S. pneumoniae pneumonia. These results suggest that SAP helps the immune system to recognise invasion by bacteria and describe a new mechanism required for control of S. pneumoniae infections. This study may help the design of new therapeutic strategies to prevent or treat important bacterial diseases. |
| اللغة: | English |
| تدمد: | 1553-7374 1553-7366 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::627b3008d914ebb36ca2a8934fee5ebb http://europepmc.org/articles/PMC1971117?pdf=render |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....627b3008d914ebb36ca2a8934fee5ebb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537374 15537366 |
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