Molecular Basis of Siglec-7 Recognition by Neisseria meningitidis Serogroup Y CPS: Implications for Immune Evasion

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Molecular Basis of Siglec-7 Recognition by Neisseria meningitidis Serogroup Y CPS: Implications for Immune Evasion

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Molecular Basis of Siglec-7 Recognition by Neisseria meningitidis Serogroup Y CPS: Implications for Immune Evasion

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

JACS Au

ISSN

2691-3704

e-ISSN

2691-3704

Svazek periodika

5

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

2257-2269

Kód UT WoS článku

001479267500001

EID výsledku v databázi Scopus

2-s2.0-105003966828