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The Lectin Pathway of Complement Activation Is a Critical Component of the Innate Immune Response to Pneumococcal Infection
The complement system plays a key role in host defense against pneumococcal infection. Three different pathways, the classical, alternative and lectin pathways, mediate complement activation. While there is limited information available on the roles of the classical and the alternative activation pa...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390405/ https://www.ncbi.nlm.nih.gov/pubmed/22792067 http://dx.doi.org/10.1371/journal.ppat.1002793 |
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author | Ali, Youssif M. Lynch, Nicholas J. Haleem, Kashif S. Fujita, Teizo Endo, Yuichi Hansen, Soren Holmskov, Uffe Takahashi, Kazue Stahl, Gregory L. Dudler, Thomas Girija, Umakhanth V. Wallis, Russell Kadioglu, Aras Stover, Cordula M. Andrew, Peter W. Schwaeble, Wilhelm J. |
author_facet | Ali, Youssif M. Lynch, Nicholas J. Haleem, Kashif S. Fujita, Teizo Endo, Yuichi Hansen, Soren Holmskov, Uffe Takahashi, Kazue Stahl, Gregory L. Dudler, Thomas Girija, Umakhanth V. Wallis, Russell Kadioglu, Aras Stover, Cordula M. Andrew, Peter W. Schwaeble, Wilhelm J. |
author_sort | Ali, Youssif M. |
collection | PubMed |
description | The complement system plays a key role in host defense against pneumococcal infection. Three different pathways, the classical, alternative and lectin pathways, mediate complement activation. While there is limited information available on the roles of the classical and the alternative activation pathways of complement in fighting streptococcal infection, little is known about the role of the lectin pathway, mainly due to the lack of appropriate experimental models of lectin pathway deficiency. We have recently established a mouse strain deficient of the lectin pathway effector enzyme mannan-binding lectin associated serine protease-2 (MASP-2) and shown that this mouse strain is unable to form the lectin pathway specific C3 and C5 convertases. Here we report that MASP-2 deficient mice (which can still activate complement via the classical pathway and the alternative pathway) are highly susceptible to pneumococcal infection and fail to opsonize Streptococcus pneumoniae in the none-immune host. This defect in complement opsonisation severely compromises pathogen clearance in the lectin pathway deficient host. Using sera from mice and humans with defined complement deficiencies, we demonstrate that mouse ficolin A, human L-ficolin, and collectin 11 in both species, but not mannan-binding lectin (MBL), are the pattern recognition molecules that drive lectin pathway activation on the surface of S. pneumoniae. We further show that pneumococcal opsonisation via the lectin pathway can proceed in the absence of C4. This study corroborates the essential function of MASP-2 in the lectin pathway and highlights the importance of MBL-independent lectin pathway activation in the host defense against pneumococci. |
format | Online Article Text |
id | pubmed-3390405 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33904052012-07-12 The Lectin Pathway of Complement Activation Is a Critical Component of the Innate Immune Response to Pneumococcal Infection Ali, Youssif M. Lynch, Nicholas J. Haleem, Kashif S. Fujita, Teizo Endo, Yuichi Hansen, Soren Holmskov, Uffe Takahashi, Kazue Stahl, Gregory L. Dudler, Thomas Girija, Umakhanth V. Wallis, Russell Kadioglu, Aras Stover, Cordula M. Andrew, Peter W. Schwaeble, Wilhelm J. PLoS Pathog Research Article The complement system plays a key role in host defense against pneumococcal infection. Three different pathways, the classical, alternative and lectin pathways, mediate complement activation. While there is limited information available on the roles of the classical and the alternative activation pathways of complement in fighting streptococcal infection, little is known about the role of the lectin pathway, mainly due to the lack of appropriate experimental models of lectin pathway deficiency. We have recently established a mouse strain deficient of the lectin pathway effector enzyme mannan-binding lectin associated serine protease-2 (MASP-2) and shown that this mouse strain is unable to form the lectin pathway specific C3 and C5 convertases. Here we report that MASP-2 deficient mice (which can still activate complement via the classical pathway and the alternative pathway) are highly susceptible to pneumococcal infection and fail to opsonize Streptococcus pneumoniae in the none-immune host. This defect in complement opsonisation severely compromises pathogen clearance in the lectin pathway deficient host. Using sera from mice and humans with defined complement deficiencies, we demonstrate that mouse ficolin A, human L-ficolin, and collectin 11 in both species, but not mannan-binding lectin (MBL), are the pattern recognition molecules that drive lectin pathway activation on the surface of S. pneumoniae. We further show that pneumococcal opsonisation via the lectin pathway can proceed in the absence of C4. This study corroborates the essential function of MASP-2 in the lectin pathway and highlights the importance of MBL-independent lectin pathway activation in the host defense against pneumococci. Public Library of Science 2012-07-05 /pmc/articles/PMC3390405/ /pubmed/22792067 http://dx.doi.org/10.1371/journal.ppat.1002793 Text en Ali et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Ali, Youssif M. Lynch, Nicholas J. Haleem, Kashif S. Fujita, Teizo Endo, Yuichi Hansen, Soren Holmskov, Uffe Takahashi, Kazue Stahl, Gregory L. Dudler, Thomas Girija, Umakhanth V. Wallis, Russell Kadioglu, Aras Stover, Cordula M. Andrew, Peter W. Schwaeble, Wilhelm J. The Lectin Pathway of Complement Activation Is a Critical Component of the Innate Immune Response to Pneumococcal Infection |
title | The Lectin Pathway of Complement Activation Is a Critical Component of the Innate Immune Response to Pneumococcal Infection |
title_full | The Lectin Pathway of Complement Activation Is a Critical Component of the Innate Immune Response to Pneumococcal Infection |
title_fullStr | The Lectin Pathway of Complement Activation Is a Critical Component of the Innate Immune Response to Pneumococcal Infection |
title_full_unstemmed | The Lectin Pathway of Complement Activation Is a Critical Component of the Innate Immune Response to Pneumococcal Infection |
title_short | The Lectin Pathway of Complement Activation Is a Critical Component of the Innate Immune Response to Pneumococcal Infection |
title_sort | lectin pathway of complement activation is a critical component of the innate immune response to pneumococcal infection |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390405/ https://www.ncbi.nlm.nih.gov/pubmed/22792067 http://dx.doi.org/10.1371/journal.ppat.1002793 |
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