Biology subjects

Marquet, S.

Publications and source records attributed to Marquet, S..

3 recordsLinked to original sources

bioRxiv2026

Single-cell characterization of the human immune landscape reveals dysfunction in monocyte-mediated cellular interactions in symptomatic malaria

Plasmodium falciparum infection results in a wide range of phenotypes including chronic asymptomatic and symptomatic individuals. The malaria outcome depends, at least in part, on host immune responses mediated by specific cell subsets. Here, we investigated the immune landscape of chronic asymptomatic and symptomatic children using single-cell RNA sequencing. Unexpectedly, we uncovered biologically relevant immune cell complexes, which were further confirmed by imaging flow cytometry. Symptomatic infection was associated with a decrease of cell-cell interactions, particularly between non-classical monocytes and T cells. Non-classical monocytes from symptomatic children exhibited profiles with increased inflammation characterized by enhanced S100A8-S100A9 expression together with decreased expression of interaction-associated genes such as CD86 or ITGAL. Moreover, we demonstrated that inflammatory and cell interaction programs could not be activated simultaneously within the same cell. In addition, the concomitant expression of inflammatory genes and members of the LILR gene family was predominantly observed in monocytes from symptomatic individuals. These findings raise the possibility that enhanced S100A8/S100A9-LILRB1 signaling may contribute to the altered functional state of monocytes in symptomatic malaria and, potentially, may impair their interactions with T cells. Together, our results suggest that immune cell complexes may therefore reveal an additional layer of immune regulation associated with the development of clinical malaria.

genomics↗

bioRxiv2025

Identification and Functional Characterization of Regulatory Variants in DPP9 Associated with COVID-19 Severity

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to a wide-range of clinical outcomes, which have been extensively studied through genome-wide association studies (GWAS). Starting from lead genetic variants associated with COVID-19 infection and severity, we identified a subset of non-coding candidate variants with potential regulatory functions. Using bioinformatics analysis and functional screening in three cell lines, we prioritized two DPP9 variants within a haplotype that increases the risk of severe COVID-19. This haplotype exhibited increased regulatory activity and altered transcription factor binding, suggesting its role in influencing COVID-19 severity through modulation of DPP9 expression in immune and lung cell types. The interest of our study lies in the functional characterization of regulatory variants responsible for the higher levels of DPP9 and lung damage observed in patients with severe COVID-19. These findings advance our understanding of genetic risk factors for COVID-19 and highlight functional SNPs that may guide future therapeutic research.

genetics↗

bioRxiv2024

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↗