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Mbow, M.

Publications and source records attributed to Mbow, M..

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↗

Mass cytometry data integration methods reveal rural-urban gradient of immune profiles across geography

The human immune system strongly varies across populations and is shaped by a wide range of host and environmental factors. As such, a rural compared to urban lifestyle has previously been associated with baseline differences in immune profiles, which can impact outcome of vaccination. The question whether there is a immune signature that associates with rural living irrespective of ancestry or geography has been addressed here along with which analytical methods are most suitable. Using three mass cytometry datasets, we studied shared and population-specific immune characteristics of healthy rural- or urban-living Indonesian, Senegalese and Tanzanian adults and urban-living Europeans. After harmonized preprocessing and quality control, 75.4 million cells were integrated using four different data-integration methods. Among these, CytoNorm with in silico references performed best, revealing shared differences in the differentiation state within the lymphocyte compartment that distinguishes rural from urban-living individuals. Differentiated CD4+ T cells expressing CTLA-4, PD-1 and ICOS characterized rural living, as did CD4+ T cells with high CD161 expression in combination with CRTH2 and GATA3. In the innate compartment, CD56- CD16 NK cells with low CD38 and CD11c expression were expanded in rural living subjects. Together, our results demonstrate that, using a harmonized analytical pipeline and machine learning-based integration, large-scale mass cytometry data can be combined across diverse cohorts to identify shared immunological hallmarks of rural living. These signatures may provide targets for modulating immune responses in future vaccine studies.

immunology↗

Phage-display immunoprecipitation sequencing reveals distinct antibody repertoire patterns across a rural-urban gradient

Environmental microbial exposures are hypothesized to drive immune profile differences across rural-urban gradients, yet direct evidence linking exposures to immune phenotypes remains limited. Here, we employed phage-displayed immunoprecipitation sequencing (PhIP-seq) to profile antibody repertoires against 357,192 epitopes from >700 organisms in 62 age-matched healthy adults from rural Senegal (n=29), urban Senegal (n=20), and urban Netherlands (n=13). PhIP-Seq analysis identified two major patterns of antibody repertoire variation: geographically restricted signatures distinguishing Senegal from the Netherlands, and a trajectory associated with rural-urban gradients spanning from rural Senegal to urban Netherlands. Integration of PhIP-seq data with high-dimensional immunological profiling revealed immune signatures correlated with the rural-urban antibody repertoire trajectory. Our findings demonstrate that antibody repertoire profiling captures distinct microbial exposure histories across both geographic regions and rural-urban gradients and correlates with variation in immune signatures. This work establishes PhIP-seq as a powerful tool for linking environmental exposure histories to population-level immune landscapes and provides insights into immune adaptation across diverse environments.

immunology↗