Molecular Basis of Siglec-7 Recognition by Neisseria meningitidis Serogroup Y CPS: Implications for Immune Evasion
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F25%3A10499139" target="_blank" >RIV/00216208:11310/25:10499139 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=pMinZUXBab" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=pMinZUXBab</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/jacsau.5c00214" target="_blank" >10.1021/jacsau.5c00214</a>
Alternative languages
Result language
angličtina
Original language name
Molecular Basis of Siglec-7 Recognition by Neisseria meningitidis Serogroup Y CPS: Implications for Immune Evasion
Original language description
Siglecs, sialic-acid-binding immunoglobulin-like lectins, are key immune cell receptors that recognize sialic acid residues on cell surfaces. Pathogens and tumor cells exploit Siglecs to evade immune responses and modulate immunity, contributing significantly to infectious disease and cancer pathogenesis. Siglec-7, primarily expressed on natural killer (NK) cells, functions as an inhibitory receptor, tightly regulating the immune activity. This study investigates the interaction between Siglec-7 and the capsular polysaccharide (CPS) of Neisseria meningitidis serogroup Y (Men-Y), a bacterium whose sialylated CPS is critical for virulence. We demonstrate that Men-Y CPS binds to inhibitory Siglec-7, potentially dampening immune recognition. We employed a multifaceted approach, combining biochemical and biophysical techniques to dissect this interaction. Enzyme-linked immunosorbent assays (ELISAs) and fluorescence titrations quantified the binding specificity and affinity. Ligand- and protein-based nuclear magnetic resonance (NMR) spectroscopy, coupled with computational modeling, provides detailed molecular insights. We highlight the critical influence of the Men-Y CPS conformation and sialic acid presentation on Siglec-7 binding. The specific arrangement of alpha-2,6-linked sialic acids on the CPS is crucial for Siglec-7 binding, demonstrating the importance of the CPS 3D structure. Preliminary immunological assays using stimulated U937 cells (a promonocytic cell line) further support the immunomodulatory role of Siglec-7 mediated by Men-Y CPS. These results offer valuable insights into the development of targeted therapeutic strategies against bacterial infections.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
JACS Au
ISSN
2691-3704
e-ISSN
2691-3704
Volume of the periodical
5
Issue of the periodical within the volume
5
Country of publishing house
US - UNITED STATES
Number of pages
13
Pages from-to
2257-2269
UT code for WoS article
001479267500001
EID of the result in the Scopus database
2-s2.0-105003966828