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dc.contributor.authorAli, Y. M.en
dc.contributor.authorLynch, N. J.en
dc.contributor.authorHaleem, K. S.en
dc.contributor.authorFujita, T.en
dc.contributor.authorEndo, Y.en
dc.contributor.authorHansen, S.en
dc.contributor.authorHolmskov, U.en
dc.contributor.authorTakahashi, K.en
dc.contributor.authorStahl, G. L.en
dc.contributor.authorDudler, T.en
dc.contributor.authorVenkatraman Girija, U.en
dc.contributor.authorWallis, R.en
dc.contributor.authorKadioglu, A.en
dc.contributor.authorStover, C. M.en
dc.contributor.authorAndrew, P. W.en
dc.contributor.authorSchwaeble, W. J.en
dc.date.accessioned2015-05-29T10:41:21Z
dc.date.available2015-05-29T10:41:21Z
dc.date.issued2012-07
dc.identifier.citationAli, Y.M. et al. (2012) The lectin pathway of complement activation is a critical component of the innate immune response to pneumococcal infection. PLoS Pathogolgy. 8 (7), e1002793en
dc.identifier.urihttp://hdl.handle.net/2086/10993
dc.description.abstractThe 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.en
dc.language.isoenen
dc.publisherPublic Library of Scienceen
dc.subjectMASP-2en
dc.subjectLectin pathway of complementen
dc.subjectPneumococcusen
dc.titleThe lectin pathway of complement activation is a critical component of the innate immune response to pneumococcal infectionen
dc.typeArticleen
dc.identifier.doihttp://dx.doi.org/10.1371/journal.ppat.1002793
dc.researchgroupInfectious Disease Research Group
dc.peerreviewedYesen
dc.fundernaen
dc.projectidnaen
dc.researchinstituteInstitute for Allied Health Sciences Researchen


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