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Mbengue, B.

Publications and source records attributed to Mbengue, B..

3 recordsLinked to original sources

A cell surface proteomic atlas reveals socioeconomic status associated immune diversity

Socioeconomic status (SES) is a potent determinant of immune variation, yet unbiased approaches to holistically map the effect of SES on the immune system are lacking. We developed a high-dimensional flow cytometry-based profiling approach to analyse 331 cell surface proteins across 33 immune cell subsets within an SES-stratified Senegalese cohort, alongside a European cohort (Netherlands). We identified 108 SES-related markers across the immune system, revealing that lower SES individuals exhibited downregulation of surface proteins, affecting in particular adhesins, chemokine and complement receptors. Conversely, lower SES was associated with hallmarks of chronic activation and exhaustion including upregulation of immune checkpoints. Metabolic profiling demonstrated that while lower SES individuals displayed elevated baseline RNA transcription, higher SES individuals exhibited superior protein translation rates. We validated these SES-related immune trends in an independent cohort and provide an interactive online resource for exploring this surface protein atlas on immune cell subsets. Taken together, these findings provide a global overview of how the cell surface proteome varies by SES, and identify molecular changes that can affect vaccine efficacy and disease outcomes.

immunology↗

Differential association of SARS-CoV-2 IgG responses with anti-OC43 IgG in a Senegalese cohort

Numerous studies elucidated the kinetics of the humoral immune response post-SARS-CoV-2 infection. However, in sub-Saharan Africa, the evolution of SARS-CoV-2 IgG antibody responses and their interaction with pre-existing seasonal human coronavirus (HCoVs: OC43, 229E, NL63, HKU1) immunity remain underexplored. A prospective cohort study was conducted in Senegal during the first year of the COVID-19 pandemic (March to December 2020). A total of 204 patients with laboratory-confirmed COVID-19 were included. Patients were classified as symptomatic (n=157) or asymptomatic (n=47) based on clinical presentation. Plasma samples (n=705) were collected over 6 months from SARS-CoV-2 positive individuals. IgG levels against SARS-CoV-2 and HCoVs were measured using a multiplex bead-based assay. Among the 204 participants included (95 [46.6%] female, median age, 44 [7-95]), SARS-CoV-2 IgG were detectable 6 months post-infection, peaking at 1 month for most antigens, except for Spike (S), which peaked at 3 months. Elderly patients (>60 years) exhibited higher IgG levels against both SARS- CoV-2 and HCoVs. Symptomatic patients had higher IgG levels than asymptomatic individuals, especially for WTS, RBD, S2, and N. Anti-HCoV IgG levels remained stable post-infection, with OC43 peaking at week 3 in symptomatic patients. A positive correlation was found between anti-SARS-CoV- 2 and anti-OC43 IgG in symptomatic patients. The study highlights persistent SARS-CoV-2 IgG antibodies for up to 6 months and suggests a link between pre-existing HCoV-OC43 immunity and COVID-19 outcomes in Senegal. These findings could help shape future vaccine strategies, considering the influence of circulating HCoVs on long- term protection against SARS-CoV-2. Author summaryUnderstanding how our immune system responds to SARS-CoV-2, the virus responsible for COVID- 19, is essential for guiding public health countermeasures and informing vaccine development strategies. In our study, we monitored, in COVID-19 patients, the evolution of IgG antibody responses against SARS-CoV-2 structural proteins over a six-month period. Additionally, we examined how previous exposure to common seasonal coronaviruses might influence immune responses to SARS-CoV-2. Conducting this research in an African context is particularly important, as data on immune responses to SARS-CoV-2 in this region are scarce. Our results provide valuable insights into the complex interplay between immune responses elicited by SARS-CoV-2 and pre-existing immunity from seasonal circulating coronaviruses. These findings enhance our understanding of immune memory and cross-reactivity, two critical factors for assessing long-term protection and optimizing vaccine strategies. By shedding light on the dynamics of antibody responses over time within a sub-Saharan population, our research contributes to the global effort aimed at developing effective interventions against COVID-19 and preparing for future coronavirus outbreaks.

immunology↗

Unraveling a novel dual-function regulatory element showing epistatic interaction with a variant that escapes genome-wide association studies.

Regulation of gene expression has recently been complexified by the identification of Epromoters, a subset of promoters with enhancer function. Here, we uncovered the first dual cis-regulatory element, "ESpromoter," exhibiting both enhancer and silencer function, as a regulator of the nearby genes ATP2B4 and LAX1 in single human T cells. Through integrative approach, we pinpointed functional rs11240391, a severe malaria risk variant that escapes detection in genome-wide association studies, challenging conventional strategies for identifying causal variants. CRISPR-modified cells demonstrated the regulatory effect of ESpromoter and rs11240391 on LAX1 expression and T cell activation. Furthermore, our findings revealed an epistatic interaction between ESpromoter SNPs and rs11240391, impacting severe malaria susceptibility by further reducing LAX1 expression. This groundbreaking discovery challenges the conventional enhancer-silencer dichotomy. It highlights the sophistication of transcriptional regulation and argues for an integrated approach combining genetics, epigenetics, and genomics to identify new therapeutic targets for complex diseases. HIGHLIGHTSO_LINovel dual enhancer-silencer element (ESpromoter) in a single human cell type C_LIO_LIFunctional SNP for severe malaria risk that escapes genome-wide association studies C_LIO_LIGenome editing at the SNP demonstrates a regulatory effect on LAX1 and T cell activation C_LIO_LIEpistatic interaction between SNPs increases the risk of severe malaria C_LI In briefEpistatic interaction between common variants within a novel dual enhancer-silencer regulatory element and the LAX1 promoter variant is responsible for severe malaria susceptibility through T-cell activation.

genomics↗