Capsular glycan recognition provides antibody-mediated protection against tuberculosis
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ABSTRACT:
PROVIDER: PRJNA594355 | ENA |
REPOSITORIES: ENA
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Project description:Increasing evidence suggests that antibodies (Abs) can have protective roles in M. tuberculosis (Mtb) infection but knowledge of the most relevant protective antigens and epitopes in humans is limited. Using novel glycan arrays, we establish that human serum IgG induced against the M. tuberculosis (Mtb) capsular polysacharide arabinomannan (AM) in natural Mtb infection is highly heterogeneous in its binding specificity and differs in both its reactivity to oligosaccharide (OS) motifs within AM and its functions between BCG vaccination and/or controlled (latent) versus uncontrolled (TB) M. tuberculosis infection. We show that anti-AM IgG from asymptomatic but not diseased individuals is protective, and provide data suggesting a role of IgG2 and specific AM oligosaccharides. Filling a gap in the current knowledge of protective antigens in humans, our human data support the key role of the M. tuberculosis surface glycan AM and suggest the importance of targeting specific glycan epitopes within AM in antibody-mediated immunity against TB.
2019-12-10 | GSE141679 | GEO
Project description: Not available
| S-EPMC7108924 | biostudies-literature
Project description:N-glycans, which represent >50% mass of the HIV-1 envelope (Env) trimer, play important roles for virus-cell entry and immune evasion. How each glycan unit interacts to shape the Env protein-sugar complex and affects Env function is not well understood. Here, high-resolution glycomics analysis of two Env variants from the same donor, with differing functional characteristics and N-glycosylation-site composition, revealed that changes to key N-glycosylation-site not only affected the Env structure at distant locations, but also had a ripple effect on Env-wide glycan processing, virus infectivity, and antibody recognition and virus neutralization. Specifically, the N262 glycan, although not located in the CD4-binding site, controlled Env binding to the CD4 receptor, affected the recognition of Env by several glycan-dependent broadly neutralizing antibodies, and altered heterogeneity of glycosylation at several sites, with N156, N160, and N448 displaying limited glycan processing. Molecular dynamic simulations visualized how specific oligosaccharide positions can move to compensate for loss of a glycan. This study demonstrates how changes in individual glycan units can alter molecular dynamics and processing of the Env-glycan shield and, consequently, Env function.
2021-09-09 | PXD017941 | Pride
Project description:The primary mechanism by which pneumococcal capsular polysaccharide-based vaccines are believed to mediate protection is by induction of serotype-specific opsonic antibodies that facilitate bacterial killing by phagocytes (opsonophagocytosis). However, antibodies that are protective against experimental pneumococcal pneumonia in mice but do not promote opsonophagocytic killing in vitro have also been identified 1-3. Such non-opsonic antibodies are associated with bacterial clearance in vivo, but the mechanism by which this occurs is unknown. In this letter, we demonstrate that a protective, non-opsonic serotype 3 pneumococcal capsular polysaccharide-specific monoclonal antibody (MAb) enhances quorum sensing, which results in competence induction and fratricide of serotype 3 pneumococcus. Gene expression profile analysis revealed that the MAb together with the pneumococcal autoinducer, competence stimulating peptide 2 (CSP2), augments differential expression of competence (com) related bacteriocin-like peptide (blp) genes that are known to be involved in pneumococcal fratricide. Taken together, these findings reveal a previously unsuspected mechanism of antibody action, namely, enhancement of quorum sensing and bacterial fratricide. Given that this activity does not require phagocytes, antibodies that function accordingly may hold promise as adjuncts to current vaccines or as desired products of next generation pneumococcal vaccines. 6 samples
2011-03-01 | E-GEOD-27258 | biostudies-arrayexpress
Project description:The primary mechanism by which pneumococcal capsular polysaccharide-based vaccines are believed to mediate protection is by induction of serotype-specific opsonic antibodies that facilitate bacterial killing by phagocytes (opsonophagocytosis). However, antibodies that are protective against experimental pneumococcal pneumonia in mice but do not promote opsonophagocytic killing in vitro have also been identified 1-3. Such non-opsonic antibodies are associated with bacterial clearance in vivo, but the mechanism by which this occurs is unknown. In this letter, we demonstrate that a protective, non-opsonic serotype 3 pneumococcal capsular polysaccharide-specific monoclonal antibody (MAb) enhances quorum sensing, which results in competence induction and fratricide of serotype 3 pneumococcus. Gene expression profile analysis revealed that the MAb together with the pneumococcal autoinducer, competence stimulating peptide 2 (CSP2), augments differential expression of competence (com) related bacteriocin-like peptide (blp) genes that are known to be involved in pneumococcal fratricide. Taken together, these findings reveal a previously unsuspected mechanism of antibody action, namely, enhancement of quorum sensing and bacterial fratricide. Given that this activity does not require phagocytes, antibodies that function accordingly may hold promise as adjuncts to current vaccines or as desired products of next generation pneumococcal vaccines.
2011-03-01 | GSE27258 | GEO
Project description:Dr. Lebrilla's lab is working on another set of transcriptomics experiments which will measure whether HMO (human milk oligosacharides) elicit a differential response on Caco2 in the presence of B.infantis. They wish to supplement the data obtained with the Illumina platform with glycan-related expression data obtained with the Gene-chips to achieve a more complete understanding on how Caco2 cells respond to the presence of HMOs and B.infantis. The transcriptomics data is being complemented by qPCR based bacterial-epithelial cells binding assays, and glycan arrays assays for which they have initiated a collaboration with the CFG Core H (David Smith).
2011-06-14 | GSE29934 | GEO
Project description:Dr. Lebrilla's lab is working on another set of transcriptomics experiments which will measure whether HMO (human milk oligosacharides) elicit a differential response on Caco2 in the presence of B.infantis. They wish to supplement the data obtained with the Illumina platform with glycan-related expression data obtained with the Gene-chips to achieve a more complete understanding on how Caco2 cells respond to the presence of HMOs and B.infantis. The transcriptomics data is being complemented by qPCR based bacterial-epithelial cells binding assays, and glycan arrays assays for which they have initiated a collaboration with the CFG Core H (David Smith). The influence, signaling and adhesion between Bifidobacterium infantis, a probiotic microorganism abundant in infant feces, and Caco2 epithelial cells. Our hypothesis is that HMOs act as signaling molecules for both Caco2 cells and B. infantis to indicate the presence in the gut, of a nutrient niche adapted for the nourishment and recruitment of HMO-consuming probiotic microorganism. HMOs therefore could play a role in the expression and binding to GBPs both on epithelial cells and in probiotic gut microorganisms. Preliminary transcriptomics data analysis obtained by using the Illumina Human Ref-8 Expression Bead Chip, has revealed that co-incubation of Caco2 cells with HMO upregulates genes belonging to chemokines, adhesion molecules, growth factors and glycan degradation, thus indicating that HMOs are actively recognized by these cells. We are working on another set of transcriptomics experiments which will measure whether HMO elicit a differential response on Caco2 in the presence of B.infantis. We wish to supplement the data obtained with the Illumina platform with glycan-related expression data obtained with the Gene-chips to achieve a more complete understanding on how Caco2 cells respond to the presence of HMOs and B.infantis. The transcriptomics data is being complemented by qPCR based bacterial-epithelial cells binding assays, and glycan arrays assays for which we have initiated a collaboration with the CFG Core H (David Smith). We are requesting the analysis of 16 RNA samples from Caco2 cells on the Glyco-gene chips, for testing respectively 4 independent biological replicates for each of the 4 different co-incubation conditions. RNA preparations from Caco2 cells were sent to Microarray Core (E). The RNA was amplified, labeled, and hybridized to GLYCO_v3 microarrays.
2011-06-14 | E-GEOD-29934 | biostudies-arrayexpress
Project description:Spheroids cultured directly from tumours can better reflect in vivo tumour characteristics than two-dimensional monolayer culture or three-dimensional culture of established cell lines. In this study, we generated antibodies by directly immunizing mice with cancer tissue-originated spheroids from colorectal cancer. We performed phenotypic screening via recognition of the surface of the spheroids and inhibition of their adhesion to extracellular matrices to identify a monoclonal antibody, clone 5G2. The antibody inhibited cell migration in two-dimensional culture and promoted cell detachment. Western blotting and immunohistochemistry detected the 5G2 signal in many colorectal cancer spheroids, as well as patient tumours, but the signal was reduced in various cell lines. The expression pattern also changed when spheroids were cultured in two-dimensional conditions. We found that 5G2 recognized the N-glycan structure, including Lea and Lec, and their major carrier proteins were CEACAM5 and CEACAM6. Translocation of integrin 4 from the lateral membrane to the extracellular matrix contact interface in the spheroids was delayed by pre-incubation with 5G2. Thus, cancer tissue-originated spheroids can be a useful antigen for generating novel anti-cancer antibodies as the glycan structure is lost in cell lines but retained in cancer tissue-originated spheroids.
2015-12-30 | GSE76405 | GEO
Project description:A novel approach toward the protection of affinity purification matrices, such as the protein streptavidin or immunoglobulins, from tryptic digestion. This allows for on-bead enzymatic digestion, while minimizing contamination from the affinity purification matrix.
2018-11-27 | MSV000083168 | MassIVE
Project description:This SuperSeries is composed of the following subset Series: GSE11944: Mucosal Glycan Foraging Enhances the Fitness and Transmission of a Saccharolytic Human Distal Gut Symbiont GSE11953: Mucosal Glycan Foraging Enhances the Fitness and Transmission of a Saccharolytic Human Distal Gut Symbiont: ECF mutant GSE11962: Growth of B. thetaiotaomicron on purified host mucosal glycans and glycan fragments Refer to individual Series
2008-11-20 | E-GEOD-11980 | biostudies-arrayexpress