Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
The lectin pathway of complement activation is a critical component of the innate immune response to pneumococcal infection
PLoS Pathogens, Volume 8, No. 7, Article e1002793, Year 2012
Notification
URL copied to clipboard!
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. © 2012 Ali et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3390405/bin/ppat.1002793.s001.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC3390405/bin/ppat.1002793.s002.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC3390405/bin/ppat.1002793.s003.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC3390405/bin/ppat.1002793.s004.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC3390405/bin/ppat.1002793.s005.pdf
Authors & Co-Authors
Ali, Youssif M.
United Kingdom, Leicester
University of Leicester
Egypt, Mansoura
Mansoura University
Lynch, Nicholas J.
United Kingdom, Leicester
University of Leicester
Haleem, Kashif S.
United Kingdom, Leicester
University of Leicester
Fujita, Teizo
Japan, Fukushima
Fukushima Medical University
Endo, Yuichi
Japan, Fukushima
Fukushima Medical University
Hansen, Søren Werner Karlskov
Denmark, Odense
Syddansk Universitet
Holmskov, Uffe
Denmark, Odense
Syddansk Universitet
Takahashi, Kazue
United States, Boston
Harvard Medical School
Stahl, Gregory L.
United States, Boston
Harvard Medical School
Dudler, Thomas
United States, Seattle
Omeros Corporation
Girija, Umakhanth V.
United Kingdom, Leicester
University of Leicester
Wallis, Russell
United Kingdom, Leicester
University of Leicester
Kadioglu, Aras
United Kingdom, Leicester
University of Leicester
United Kingdom, Liverpool
University of Liverpool
Stover, Cordula M.
United Kingdom, Leicester
University of Leicester
Andrew, Peter W.
United Kingdom, Leicester
University of Leicester
Schwaeble, Wilhelm J.
United Kingdom, Leicester
University of Leicester
Statistics
Citations: 166
Authors: 16
Affiliations: 7
Identifiers
Doi:
10.1371/journal.ppat.1002793
ISSN:
15537366
e-ISSN:
15537374