Biology subjects

Mouton, W.

Publications and source records attributed to Mouton, W..

5 recordsLinked to original sources

bioRxiv2026

Functional alterations of immune gene expression in ICU and non-ICU patients with Legionnaires' disease, a prospective observational study

Legionnaires disease (LD), a pneumonia caused by Legionella pneumophila intracellular bacterium, leads to intensive care unit (ICU) admission in 20-40% of cases. While these ICU-LD patients display severe lung injury or septic shock, their functional immune response remains poorly understood. The present study aimed, through a large immune gene expression assessment, to improve the understanding of immune cell functionality after whole blood LPS ex vivo stimulation in ICU-LD patients compared with non-ICU. Both ICU and non-ICU-LD displayed altered gene expression indicating that both patients immune cells are less able to respond to the LPS ex vivo stimulus than a healthy population. ICU-LD patients had 1.6-fold greater number of less-expressed genes (35/93 vs 22/93, p=0.039), and lower Log2(FC) of these genes (median [IQR]: -1.9 [-2.6;-1.5] vs -1.2 [-1.7;-0.9], p=0.0011) than non-ICU-LD. Seven genes were significantly less expressed by ICU-LD patients (IRF7, MX1, NFKBI2, NFKBIA, RELB, SRC, TIM3; p-value range: 0.029-0.0080). Top five gene ontology biological processes, subcellular localisations, and reactome pathways (STRING database) uniquely enriched in ICU-LD-patients and related less-expressed genes were cellular response to LPS (CCL2, NFKBIA, IRAK2, TIM3, SRC, NFKB1), regulation of IFN-{beta} production (IRF7, RIG1, OAS2, RELB), I-{kappa}B/NF-{kappa}B complex (NFKBIA, NFKB1, NFKB2), IFN regulatory factor complex (RIG1, IRF7), and TRAF6-mediated NF-{kappa}B activation pathway (NFKBIA, NFKB1, NFKB2, RIG1). Immune gene expression alterations in LD after LPS stimulation were found herein, with more pronounced alterations in ICU-LD patients. A reduced expression of key genes and pathways involved in controlling Legionella proliferation in ICU-LD patients may contribute to increased disease severity.

immunology↗

bioRxiv2025

Immunological and clinical markers of post-acute sequelae of COVID-19: Insights from mild and severe cases six months post-infection

Post-acute sequelae of COVID-19 (PASC) is a complex and multifaceted clinical challenge requiring to emphasize its underlying pathophysiological mechanisms. This study assessed hundreds of virological, serological, immunological, and tissue damage biomarkers in two patient cohorts who experienced mild (n=270) or severe (n=188) COVID-19, 6 to 9 months post-initial infection, and in which 40% and 57.4% of patients, respectively, developed PASC. Blood analysis showed that mains differences observed in humoral, viral, and biological biomarkers were associated with the initial COVID-19 severity, rather than being specifically linked to PASC. However, patients with PASC displayed altered CD4+ and CD8+ memory T-cell subsets, with higher cytokine-secreting cells and increased terminally differentiated CD45RA+ effector memory T cells (TEMRA). Elevated SARS-CoV-2-specific T cells responsive to nucleocapsid/membrane proteins with a TEMRA phenotype were also observed. A random forest model identified these features and initial symptom duration as top variables discriminating PASC, achieving over 80% classification accuracy. HighlightsO_LINine months post-initial SARS-CoV-2 infection, over 40% of patients developed PASC C_LIO_LIRegardless of PASC, the initial disease form influenced the main immune differences C_LIO_LIPASC led to altered memory T-cell subsets with elevated TEMRA phenotype C_LIO_LIPASC presence is associated with disease form, initial symptom count and duration C_LI

immunology↗

bioRxiv2023

Staphylococcus aureus can use an alternative pathway to be internalized by osteoblasts in absence of β1 integrins

Staphylococcus aureus main internalization mechanism in osteoblasts relies on a tripartite interaction between bacterial fibronectin-binding proteins, extracellular matrix soluble fibronectin, and osteoblasts {beta}1 integrins. Caveolins, and particularly caveolin-1, have shown to limit the plasma membrane microdomain mobility, and consequently reduce the uptake of S. aureus in keratinocytes. In this study, we aimed to deepen our understanding of the molecular mechanisms underlying S. aureus internalization in osteoblasts. Mechanistically, S. aureus internalization requires endosomal recycling {beta}1 integrins as well as downstream effectors such as Src, Rac1, and PAK1. Surprisingly, in {beta}1 integrin deficient osteoblasts, S. aureus internalization is restored when Caveolin-1 is absent and requires v{beta}3/v{beta}5 integrins as backup fibronectin receptors. Altogether, our data support that {beta}1 integrins regulate the level of detergent-resistant membrane at the plasma membrane in a an endosomal and Caveolin-1 dependent manner. SUMMARY STATEMENTStaphylococcus aureus can be internalized by osteoblasts via a different mechanism than the main 5{beta}1/fibronectin/fibronectin-binding protein that likely involves v{beta}3 or v{beta}5 integrin.

cell biology↗

bioRxiv2019

Towards standardization of immune functional assays

Recent advances in the immunotherapy field require evaluation of the immune function to adapt therapeutic decisions. Immune functional assays (IFA) are able to reveal the immune status and would be useful to further adapt/improve patients care. However, standardized methods are needed to implement IFA in clinical settings. We carried out an independent validation of a published method used to characterize the underlying host response to infectious conditions using an IFA. We evaluate the reproducibility and robustness of this IFA and associated readout using an independent healthy volunteers (HV) cohort. Expression of a 44 genes-signatures and IFN{gamma} protein secretion and gene-expression was assessed after stimulation. We observed a strong host-response correlation between the two cohorts. We also highlight that standardized methods for immune function evaluation exist and could be implemented in larger-scale studies. This IFA could be a relevant tool to reveal innate/adaptive immune dysfunction in immune-related disorders patients.

immunology↗

bioRxiv2016

Clinical metagenomics of bone and joint infections: a proof of concept study

BackgroundBone and joint infections (BJI) are severe infections that require a tailored and protracted antibiotic treatment. The diagnostic of BJI relies on the culture of surgical specimens, yet some bacteria would not grow because of extreme oxygen sensitivity or fastidious growth. Hence, metagenomic sequencing could potentially address those limitations. In this study, we assessed the performances of metagenomic sequencing of BJI samples for the identification of pathogens and the prediction of antibiotic susceptibility.\n\nMethodsA total of 179 samples were considered. The DNA was extracted with a kit aiming to decrease the amount of human DNA (Molzym), and sequenced on an Illumina HiSeq2500 in 2x250 paired-end reads. The taxonomy was obtained by MetaPhlAn2, the bacterial reads assembled with MetaSPAdes and the antibiotic resistance determinants (ARDs) identified using a database made of Resfinder+ARDs from functional metagenomic studies.\n\nResultsWe could sequence the DNA from 24 out of 179 samples. For monomicrobial samples (n=8), the presence of the pathogen was confirmed by metagenomics in all cases. For polymicrobial samples (n=16), 32/55 bacteria (58.2%) were found at the species level (41/55 [74.5%] at the genus level). Conversely, a total of 273 bacteria not found in culture were identified, 182 being possible pathogens undetected in culture and 91 contaminants. A correct antibiotic susceptibility could be inferred in 94.1% cases for monomicrobial samples and in 76.5% cases in polymicrobial samples.\n\nConclusionsWhen sufficient amounts of DNA can be extracted from samples, we found that clinical metagenomics is a potential tool to support conventional culture.

microbiology↗