Biology subjects

Jamin, C.

Publications and source records attributed to Jamin, C..

3 recordsLinked to original sources

bioRxiv2021

IL-21 and IFN-α have both opposite and redundant role on human innate precursors and memory B-cell differentiation.

Immunological memory is essential for effective immune protection upon antigen rechallenge. Memory B cells encompass multiple subsets, heterogeneous in terms of phenotypes, origins and precursors, anatomical localization, and functional responses. B-cell responses are conditioned by micro-environmental signals, including cytokines. Here, we analyzed in vitro the effects of two cytokines implicated in B-cell differentiation, interferon-alpha (IFN-) and interleukin (IL)-21, on the early functional response of four different mature B-cell subsets (IgD- CD27- naive, IgD+ CD27+ unswitched, IgD- CD27+ switched and double-negative B cells). The dual response of naive and memory B cells to IL-21 allowed us to uncover a unique IgD+ CD27- CD10- B-cell population (referred to as NARB+) characterized by the expression of marginal zone B-cell markers CD45RB and CD1c. Similar to memory B cells, NARB+ cells were in a pre-activated state, allowing them to rapidly differentiate into plasmablasts upon innate signals while maintaining their susceptibility to IL-21 activation-induced apoptosis as observed for the naive compartment. Both in-depth phenotypic analysis of circulating B cells, and identification of these cells in spleen, tonsil and gut-associated lymphoid tissues, supported that NARB+ are uncommitted precursors of human marginal zone B cells.

immunology↗

bioRxiv2020

Harmonization of whole genome sequencing for outbreak surveillance of Enterobacteriaceae and Enterococci

Whole genome sequencing (WGS), is becoming the facto standard for bacterial typing and outbreak surveillance of resistant bacterial pathogens. We performed a three-center ring trial to assert if inter-laboratory harmonization of WGS is achievable, for this goal. To this end, a set of 30 bacterial isolates comprising of various species belonging to the Enterobacteriaceae and Enterococcus genera were selected and sequenced using the same protocol on the Illumina MiSeq platform in each individual centre. All generated sequencing data was analysed by 1 centre using BioNumerics (6.7.3) for i) genotyping origin of replications & antimicrobial resistance genes, ii) core-genome (cgMLST) for E. coli and K. pneumoniae & whole-genome multi locus sequencing typing (wgMLST) for all species. Additionally, a split k-mer analysis was performed to determine the number of SNPs between samples. A precision of 99.0% and an accuracy of 99.2% was achieved for genotyping. Based on cgMLST, only in 2/27 and 3/15 comparisons a discrepant allele was called between two genomes, for E. coli and K. pneumonia, respectively. Based on wgMLST, the number of discrepant alleles ranged from 0 to 7 (average 1.6). For SNPs, this ranged from 0-11 SNPs (average 3.4). Furthermore, we demonstrate that using different de novo assemblers to analyse the same dataset introduces up to 150 SNPs, which surpasses most thresholds for bacterial outbreaks. This shows the importance of harmonisation of data processing surveillance of bacterial outbreaks. Summarizing, multi-center WGS for bacterial surveillance is achievable, but only if protocols are harmonized.

microbiology↗

bioRxiv2020

Higher prevalence of Bacteroides fragilis in Crohn's disease exacerbations and strain-dependent increase of epithelial resistance

Bacteroides fragilis has previously been linked to Crohns disease (CD) exacerbations, but results are inconsistent and underlying mechanisms unknown. This study investigates the epidemiology of B. fragilis and its virulence factors bft (enterotoxin) and ubiquitin among 181 CD patients and the impact on the intestinal epithelial barrier in vitro. The prevalence of B. fragilis was significantly higher in active (n=69/88, 78.4%) as compared to remissive (n=58/93, 62.4%, p=0.018) CD patients. Moreover, B. fragilis was associated with intestinal strictures. Interestingly, the intestinal barrier function, as examined by transepithelial electrical resistance (TEER) measurements of Caco-2 monolayers, improved when exposed to secretomes of bft-positive (increased TEER [~]160%, p<0.001) but not when exposed to bft- negative strains. Whole metagenome sequencing and metabolomics, respectively, identified 19 coding sequences and two metabolites that discriminated TEER-increasing from non-TEER-increasing strains. This study revealed a higher B. fragilis prevalence during exacerbation. Surprisingly, bft-positive secretomes improved epithelial resistance.

microbiology↗