The bacterial pathogen binds to the C-type lectin DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin) on dendritic cells to evade the immune system. While DC-SIGN glycoconjugate ligands are ubiquitous among mycobacterial species, the receptor selectively binds pathogenic species from the complex (). Here, we unravel the molecular mechanism behind this intriguing selective recognition by means of a multidisciplinary approach combining single-molecule atomic force microscopy with Förster resonance energy transfer and bioassays. Molecular recognition imaging of mycobacteria demonstrates that the distribution of DC-SIGN ligands markedly differs between Bacille Calmette-Guérin (BCG) (model species) and (non- species), the ligands being concentrated into dense nanodomains on BCG. Upon bacteria-host cell adhesion, ligand nanodomains induce the recruitment and clustering of DC-SIGN. Our study highlights the key role of clustering of both ligands on species and DC-SIGN host receptors in pathogen recognition, a mechanism that might be widespread in host-pathogen interactions.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10198640 | PMC |
| http://dx.doi.org/10.1126/sciadv.adf9498 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Host cell lectins ASGR1 and DC-SIGN jointly with TMEM106B confer ACE2 independence and imdevimab resistance to SARS-CoV-2 pseudovirus with spike mutation E484D.
J Virol
January 2025
Infection Biology Unit, German Primate Centre - Leibniz Institute for Primate Research, Göttingen, Germany.
The naturally occurring mutation E484D in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can render viral entry ACE2 independent and imdevimab resistant. Here, we investigated whether the cellular proteins ASGR1, DC-SIGN, and TMEM106B, which interact with the viral S protein, can contribute to these processes. Employing S protein-pseudotyped particles, we found that expression of ASGR1 or DC-SIGN jointly with TMEM106B allowed for robust entry of mutant E484D into otherwise non-susceptible cells, while this effect was not observed upon separate expression of the single proteins and upon infection with SARS-CoV-2 wild type (WT).
View Article and Find Full Text PDFLimitations of a proper SFTSV mouse model using human C-type lectin receptors.
Front Microbiol
December 2024
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne virus with a human mortality rate of up to 30%, posing a significant threat to public health. However, the lack of suitable research models has impeded the development of effective human vaccines. In this study, we engineered transgenic mice (3xTg) using a novel construct that simultaneously expresses three C-type Lectin receptors, identified as critical SFTSV entry receptors.
View Article and Find Full Text PDFLactobacillus crispatus S-layer proteins modulate innate immune response and inflammation in the lower female reproductive tract.
Nat Commun
December 2024
Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Department of Metabolism Digestion and Reproduction, Imperial College London, London, UK.
Lactobacillus species dominance of the vaginal microbiome is a hallmark of vaginal health. Pathogen displacement of vaginal lactobacilli drives innate immune activation and mucosal barrier disruption, increasing the risks of STI acquisition and, in pregnancy, of preterm birth. We describe differential TLR mediated activation of the proinflammatory transcription factor NF-κB by vaginal pathogens and commensals.
View Article and Find Full Text PDFCarbohydrate-mediated interactions between chloroviruses and the immune system.
Commun Biol
December 2024
Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Understanding the molecular mechanisms which drive and modulate host-pathogen interactions are essential when designing effective therapeutic and diagnostic approaches aimed at controlling infectious diseases. Certain large and giant viruses have recently been discovered as components of the human virome, yet little is known about their interactions with the host immune system. We have dissected the role of viral N-linked glycans during the interaction between the glycoproteins from six chloroviruses (belonging to three chlorovirus classes: NC64A, SAG, and Osy viruses) and the representative carbohydrate-binding receptors of the innate immune system.
View Article and Find Full Text PDFThe tissue glycome as regulator of immune activation and tolerance mediated by C-type lectins and Siglecs.
Semin Immunol
November 2024
Amsterdam UMC location Vrije Universiteit Amsterdam, Molecular Cell Biology and Immunology, De Boelelaan, Amsterdam 1117, The Netherlands; Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, The Netherlands; Amsterdam institute for Infection and Immunity, Cancer Immunology, Amsterdam, The Netherlands. Electronic address:
The immune system is a complex network of highly specialized microenvironments, denominated niches, which arise from dynamic interactions between immune and parenchymal cells as well as acellular components such as structural elements and local molecular signals. A critical, yet underexplored, layer shaping these niches is the glycome, the complete repertoire of glycans and glycoconjugates produced by cells. The glycome is prevalent in the outer membrane of cells and their secreted components, and can be sensed by glycan binding receptors on immune cells.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!