Biology subjects

Corvol, H.

Publications and source records attributed to Corvol, H..

3 recordsLinked to original sources

bioRxiv2025

The epigenomic landscape of bronchial epithelial cells reveals the establishment of trained immunity

BackgroundInnate immune memory, also called trained immunity, refers to the ability of innate immune cells to gain memory characteristics after transient stimulation, resulting in a nonspecific modified inflammatory response upon secondary remote challenge. Bronchial epithelial cells (BECs) participate in innate immune defence and are the first cells of the lower respiratory tract to encounter inhaled pathogens. We recently showed that BECs are capable of innate immune memory after preexposure to Pseudomonas aeruginosa flagellin through epigenetic mechanisms. In the present study, we investigated such mechanisms through the modification of chromatin architecture induced by flagellin preexposure that results in subsequent changes of gene expression. ResultsBy conducting an unsupervised approach to jointly analyse chromatin accessibility and gene expression, we mapped the remodelling of the epigenomic and transcriptomic profiles during the establishment of BECs memory. We identified a Memory regulatory profile induced by flagellin exposure. It includes clusters of upregulated genes related to inflammation that are linked to a sustainable gain in chromatin accessibility and with an increased activity of specific factors (TFs) whose binding may drive this process. ConclusionsIn summary, we demonstrated that flagellin exposure induced changes in chromatin condensation in BECs, which sustains the reprogramming of transcriptional patterns

genetics↗

bioRxiv2021

Leveraging TOPMed Imputation Server and Constructing a Cohort-Specific Imputation Reference Panel to Enhance Genotype Imputation among Cystic Fibrosis Patients

Cystic fibrosis (CF) is a severe genetic disorder that can cause multiple comorbidities affecting the lungs, the pancreas, the luminal digestive system and beyond. In our previous genome-wide association studies (GWAS), we genotyped [~]8,000 CF samples using a mixture of different genotyping platforms. More recently, the Cystic Fibrosis Genome Project (CFGP) performed deep ([~]30x) whole genome sequencing (WGS) of 5,095 samples to better understand the genetic mechanisms underlying clinical heterogeneity among CF patients. For mixtures of GWAS array and WGS data, genotype imputation has proven effective in increasing effective sample size. Therefore, we first performed imputation for the [~]8,000 CF samples with GWAS array genotype using the TOPMed freeze 8 reference panel. Our results demonstrate that TOPMed can provide high-quality imputation for CF patients, boosting genomic coverage from [~]0.3 - 4.2 million genotyped markers to [~]11 - 43 million well-imputed markers, and significantly improving Polygenic Risk Score (PRS) prediction accuracy. Furthermore, we built a CF-specific CFGP reference panel based on WGS data of CF patients. We demonstrate that despite having [~]3% the sample size of TOPMed, our CFGP reference panel can still outperform TOPMed when imputing some CF disease-causing variants, likely due to allele and haplotype differences between CF patients and general populations. We anticipate our imputed data for 4,656 samples without WGS data will benefit our subsequent genetic association studies, and the CFGP reference panel built from CF WGS samples will benefit other investigators studying CF.

genetics↗

bioRxiv2020

Flagellin from Pseudomonas aeruginosa increases the expression of the SARS-CoV2 entry protease TMPRSS2 in airway epithelial cells

The major challenge of the COVID-19 health crisis is to identify the factors of susceptibility to SARS-Cov2 in order to adapt the recommendations to the populations and to reduce the risk of getting COVID-19 to the most vulnerable people especially those having chronic respiratory diseases including cystic fibrosis (CF). Airway epithelial cells (AEC) are playing a critical role in the immune response and in COVID-19 severity. SARS-CoV-2 infects the airways through ACE2 receptor and the host protease TMPRSS2 was shown to play a major role in SARS-CoV-2 infectivity. Here, we show that the main component of P. aeruginosa flagella, ie. flagellin is able to increase TMPRSS2 expression in AEC, and even more in those deficient for CFTR. Importantly, this increased TMPRSS2 expression is associated with an increase in the level of SARS-CoV-2 infection. Considering the urgency of the health situation, this result is of major significance for patients with CF which are frequently infected and colonized by P. aeruginosa during the course of the disease.

pathology↗