Binding of mannan-binding protein to various bacterial pathogens of meningitis

Emmerik, L. C. Van; Kuijper, Ed J.; Fijen, C. A. P.; Dankert, J.; Thiel, Steffen

doi:10.1111/j.1365-2249.1994.tb06103.x

Cited by 97 publications

(42 citation statements)

References 32 publications

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“…2B and 2C). MBL did not bind to any bacteria tested, a finding consistent with previous observations (36,45). All strains to which L-ficolin/MASP complexes bound consumed C4 (Fig.…”

Section: Binding Of L-ficolin/masp and Mbl/masp Complexes To Intact Gsupporting

confidence: 91%

“…One of these MASP, MASP-2, cleaves C4 and C2 to generate the C4b2a complex (40). Although it has been shown that L-ficolin binds to serotype III GBS CPS (3) and lipoteichoic acid (LTA) (29) and that MBL has low affinity for GBS (36,45), the studies were performed with restricted numbers of GBS strains. The ligand for both L-ficolin and MBL, N-acetylglucosamine (GlcNAc), is one of five monosaccharides incorporated into the CPS of GBS belonging to all serotypes (17-19, 21, 49-51) except serotype VI CPS (46) and serotype VIII CPS (20) and is a constituent of the group B-specific polysaccharide (GBPS) (33).…”

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confidence: 99%

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L-Ficolin/Mannose-Binding Lectin-Associated Serine Protease Complexes Bind to Group B Streptococci Primarily throughN-Acetylneuraminic Acid of Capsular Polysaccharide and Activate the Complement Pathway

et al. 2008

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Group B streptococci (GBS) are the most common cause of neonatal sepsis and meningitis. Most infants who are colonized with GBS at birth do not develop invasive disease, although many of these uninfected infants lack protective levels of capsular polysaccharide (CPS)-specific antibody. The lectin pathway of complement is a potential mechanism for initiating opsonization of GBS with CPS-specific antibody-deficient serum. In this study, we determined whether mannose-binding lectin (MBL)/MBL-associated serine protease (MASP) complexes and L-ficolin/MASP complexes bind to different strains of GBS to activate the lectin pathway, and we identified the molecules recognized by lectins on the GBS surface. We found that MBL did not bind to any GBS examined, whereas L-ficolin bound to GBS cells of many serotypes. L-ficolin binding to GBS cells correlated with the CPS content in serotypes Ib, III (restriction digestion pattern types III-2 and III-3), and V but not with the group B-specific polysaccharide (GBPS) content or with the lipoteichoic acid (LTA) content. L-ficolin bound to purified CPS and GBPS in a concentration-dependent manner but not to purified LTA. All strains to which L-ficolin/MASP complexes bound consumed C4. When N-acetylneuraminic acid (NeuNAc) was selectively removed from GBS cells by treatment with neuraminidase, the reduction in L-ficolin binding was correlated with the amount of NeuNAc removed. Additionally, L-ficolin was able to bind to wild-type strains but was able to bind only weakly to unencapsulated mutants and a mutant strain in which the CPS lacks NeuNAc. We concluded that L-ficolin/MASP complexes bind to GBS primarily through an interaction with NeuNAc of CPS.

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“…2B and 2C). MBL did not bind to any bacteria tested, a finding consistent with previous observations (36,45). All strains to which L-ficolin/MASP complexes bound consumed C4 (Fig.…”

Section: Binding Of L-ficolin/masp and Mbl/masp Complexes To Intact Gsupporting

confidence: 91%

mentioning

confidence: 99%

L-Ficolin/Mannose-Binding Lectin-Associated Serine Protease Complexes Bind to Group B Streptococci Primarily throughN-Acetylneuraminic Acid of Capsular Polysaccharide and Activate the Complement Pathway

et al. 2008

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“…The classical and lectin pathways display similar activation of C2, but our data indicate no activation by the lectin pathway of any importance, since similar results were obtained in MBL-sufficient and MBL-deficient individuals. This is in accordance with previously published results (7,21,46). These results are also in accordance with the well-established role of antibodies to effectively protect against meningococcal disease (14,16,20).…”

Section: Discussionsupporting

confidence: 93%

Critical Roles of Complement and Antibodies in Host Defense Mechanisms againstNeisseria meningitidisas Revealed by Human Complement Genetic Deficiencies

et al. 2010

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Certain complement defects are associated with an increased propensity to contract Neisseria meningitidis infections. We performed detailed analyses of complement-mediated defense mechanisms against N. meningitidis 44/76 with whole blood and serum from two adult patients who were completely C2 or C5 deficient. The C5-deficient patient and the matched control were also deficient in mannose-binding lectin (MBL). The proliferation of meningococci incubated in freshly drawn whole blood was estimated by CFU and quantitative DNA real-time PCR. The serum bactericidal activity and opsonophagocytic activity by granulocytes were investigated, including heat-inactivated postvaccination sera, to examine the influence of antimeningococcal antibodies. The meningococci proliferated equally in C2-and C5-deficient blood, with a 2 log 10 increase of CFU and 4-to 5-log 10 increase in DNA copies. Proliferation was modestly decreased in reconstituted C2-deficient and control blood. After reconstitution of C5-deficient blood, all meningococci were killed, which is consistent with high antibody titers being present. The opsonophagocytic activity was strictly C2 dependent, appeared with normal serum, and increased with postvaccination serum. Serum bactericidal activity was strictly dependent on C2, C5, and high antibody titers. MBL did not influence any of the parameters observed. Complement-mediated defense against meningococci was thus dependent on the classical pathway. Some opsonophagocytic activity occurred despite low levels of antimeningococcal antibodies but was more efficient with immune sera. Serum bactericidal activity was dependent on C2, C5, and immune sera. MBL did not influence any of the parameters observed.

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“…Consistent with the wide array of infections reported in persons with MBL deficiency, several in vitro studies have demonstrated that MBL binds to a diverse spectrum of pathogens and that bound MBL can promote C4 deposition on the pathogen surface (116,181,226,231,318,465,481). Such studies have prompted investigators to link MBL deficiency with infections, and this is discussed next.…”

Section: Inherited Deficiencies Of Complement Activationmentioning

confidence: 67%

Infections of People with Complement Deficiencies and Patients Who Have Undergone Splenectomy

2010

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SUMMARY The complement system comprises several fluid-phase and membrane-associated proteins. Under physiological conditions, activation of the fluid-phase components of complement is maintained under tight control and complement activation occurs primarily on surfaces recognized as “nonself” in an attempt to minimize damage to bystander host cells. Membrane complement components act to limit complement activation on host cells or to facilitate uptake of antigens or microbes “tagged” with complement fragments. While this review focuses on the role of complement in infectious diseases, work over the past couple of decades has defined several important functions of complement distinct from that of combating infections. Activation of complement in the fluid phase can occur through the classical, lectin, or alternative pathway. Deficiencies of components of the classical pathway lead to the development of autoimmune disorders and predispose individuals to recurrent respiratory infections and infections caused by encapsulated organisms, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. While no individual with complete mannan-binding lectin (MBL) deficiency has been identified, low MBL levels have been linked to predisposition to, or severity of, several diseases. It appears that MBL may play an important role in children, who have a relatively immature adaptive immune response. C3 is the point at which all complement pathways converge, and complete deficiency of C3 invariably leads to severe infections, including those caused by meningococci and pneumococci. Deficiencies of the alternative and terminal complement pathways result in an almost exclusive predisposition to invasive meningococcal disease. The spleen plays an important role in antigen processing and the production of antibodies. Splenic macrophages are critical in clearing opsonized encapsulated bacteria (such as pneumococci, meningococci, and Escherichia coli) and intraerythrocytic parasites such as those causing malaria and babesiosis, which explains the fulminant nature of these infections in persons with anatomic or functional asplenia. Paramount to the management of patients with complement deficiencies and asplenia is educating patients about their predisposition to infection and the importance of preventive immunizations and seeking prompt medical attention.

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Binding of mannan-binding protein to various bacterial pathogens of meningitis

Cited by 97 publications

References 32 publications

L-Ficolin/Mannose-Binding Lectin-Associated Serine Protease Complexes Bind to Group B Streptococci Primarily throughN-Acetylneuraminic Acid of Capsular Polysaccharide and Activate the Complement Pathway

L-Ficolin/Mannose-Binding Lectin-Associated Serine Protease Complexes Bind to Group B Streptococci Primarily throughN-Acetylneuraminic Acid of Capsular Polysaccharide and Activate the Complement Pathway

Critical Roles of Complement and Antibodies in Host Defense Mechanisms againstNeisseria meningitidisas Revealed by Human Complement Genetic Deficiencies

Infections of People with Complement Deficiencies and Patients Who Have Undergone Splenectomy

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