Biology subjects

Marcon, F.

Publications and source records attributed to Marcon, F..

3 recordsLinked to original sources

bioRxiv2025

Long Non-Coding RNAs in Response to Ebola Virus Vaccine-Induced Immunity

Long noncoding RNAs (lncRNAs) have emerged as critical regulators of gene expression, yet their role in shaping human responses to vaccination remains largely uncharacterized. Here, we analyzed RNA-sequencing data from three independent human cohorts vaccinated with the rVSV{Delta}G-ZEBOV-GP Ebola vaccine to profile lncRNA expression dynamics. Using differential expression analysis and correlation meta-analysis across cohorts, we identified an expression signature with several lncRNAs, including LEF1-AS1 and DOCK8-AS1, that exhibit conserved transcriptional activation following vaccination. Correlation of lncRNA expression with gene targets and IgG titers revealed putative roles for lncRNAs in regulating and/or participate in both innate immune responses and adaptive antibody production. Functional enrichment of lncRNA co-expressed protein-coding genes highlighted involvement in T-cell differentiation, interferon signaling, and leukocyte activation. Integrating global run-on sequencing data and comparative transcriptomic analysis across other vaccine studies suggests that LEF1-AS1 modulation is distinctively associated with Ebola vaccination. Our findings demonstrate that lncRNAs are potential integral components of the human vaccine response and provide a foundation for future mechanistic studies targeting noncoding RNA regulation of immunity SignificanceEbola virus remains a significant global health threat due to its high mortality rate and potential for widespread outbreaks, underscoring the urgent need for effective and durable vaccines to control future epidemics. Understanding the transcriptional mechanisms underlying immune responses to vaccination is important to improving vaccine design and efficacy. While protein-coding genes have been extensively studied, the role of long noncoding RNAs (lncRNAs) in vaccine-induced immunity remains poorly understood. Here, we characterize the dynamics of lncRNA expression following administration of the rVSV{Delta}G-ZEBOV-GP Ebola vaccine across multiple human cohorts and identify conserved lncRNA signatures associated with both innate and adaptive immunity. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=154 SRC="FIGDIR/small/671152v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@25581aorg.highwire.dtl.DTLVardef@1bb31cforg.highwire.dtl.DTLVardef@c3299eorg.highwire.dtl.DTLVardef@e176b9_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2023

Spatial determination and prognostic impact of the fibroblast transcriptome in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma has a poor clinical outcome and responses to immunotherapy are suboptimal. Stromal fibroblasts are a dominant but heterogenous population within the tumor microenvironment and therapeutic targeting of stromal subsets may have therapeutic utility. Here we combined spatial transcriptomics and scRNA-Seq to define the transcriptome of tumor-proximal and tumor-distal cancer-associated fibroblasts (CAFs) and linked this to clinical outcome. Tumor-proximal fibroblasts comprised large populations of myofibroblasts, strongly expressed podoplanin, and were enriched for Wnt ligand signaling. In contrast, inflammatory CAFs were dominant within tumor-distal subsets and expressed complement components and the Wnt-inhibitor SFRP2. Poor clinical outcome was correlated with elevated HIF-1 and podoplanin whilst high level expression of inflammatory and complement genes was predictive of extended survival. These findings demonstrate the extreme transcriptional heterogeneity of CAFs and its determination by apposition to tumor. Selective targeting of tumor-proximal subsets, potentially combined with HIF-1 inhibition and immune stimulation, may offer a multimodal therapeutic approach for this disease. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=170 SRC="FIGDIR/small/524883v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@b34606org.highwire.dtl.DTLVardef@1ba47c3org.highwire.dtl.DTLVardef@bd75f1org.highwire.dtl.DTLVardef@8a602b_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2018

Inflammation induced by influenza virus impairs innate control of human pneumococcal carriage

Secondary bacterial pneumonia following influenza infection is a significant cause of mortality worldwide. Upper respiratory tract pneumococcal carriage is important as both determinants of disease and population transmission. The immunological mechanisms that contain pneumococcal carriage are well-studied in mice but remain unclear in humans. Loss of this control of carriage following influenza infection is associated with secondary bacterial pneumonia during seasonal and pandemic outbreaks. We used a human type 6B pneumococcal challenge model to show that carriage acquisition induces early degranulation of resident neutrophils and recruitment of monocytes to the nose. Monocyte function associated with clearance of pneumococcal carriage. Prior nasal infection with live attenuated influenza virus induced inflammation, impaired innate function and altered genome-wide nasal gene responses to pneumococcal carriage. Levels of the cytokine IP-10 promoted by viral infection at the time of pneumococcal encounter was positively associated with bacterial density. These findings provide novel insights in nasal immunity to pneumococcus and viral-bacterial interactions during co-infection.

immunology↗