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Bodinier, M.

Publications and source records attributed to Bodinier, M..

2 recordsLinked to original sources

RNA-seq transcriptome analysis reveals LTR-retrotransposons modulation in Human Peripheral Blood Mononuclear Cells (PBMCs) after in vivo Lipopolysaccharides (LPS) injection

Human Endogenous Retroviruses (HERVs) and Mammalian apparent LTR-retrotransposons (MaLRs) are retroviral sequences that integrated into the germline cells millions year ago. Transcripts of these LTR-retrotransposons are present in several tissues, and their expression is modulated in pathological conditions, although their function remains often far from being understood. In this work, we focused on the HERVs/MaLRs expression and modulation in a scenario of immune system activation. We used a public dataset of Human Peripheral Blood Mononuclear Cells (PBMCs) RNA-seq from 15 healthy participants to a clinical trial before and after the exposure to Lipopolysaccharide (LPS), for which we established an RNA-seq workflow for the identification of expressed and modulated cellular genes and LTR-retrotransposon elements. ImportanceWe described the HERV and MaLR transcriptome in PBMCs, finding that about 8.4 % of the LTR-retrotransposons loci were expressed, and identifying the betaretrovirus-like HERVs as those with the highest percentage of expressed loci. We found 4,607 HERVs and MaLRs loci that were modulated as a result of in vivo stimulation with LPS. The HERV-H group showed the highest number of differentially expressed most intact proviruses. We characterized the HERV and MaLR loci differentially expressed checking their genomic context of insertion and, interestingly, we found a general co-localization with genes that are involved and modulated in the immune response, as consequence of LPS stimulation. The analyses of HERVs and MaLRs expression and modulation show that this LTR-retrotransposons are expressed in PBMCs and regulated in inflammatory settings. The similar regulation of HERVs/MaLRs and genes after LPS stimulation suggests possible interactions of LTR-retrotransposons and the immune host response.

microbiology↗

Transplacentally mediated immune training to accelerate fetal immune competence

We recently reported that the offspring of mice treated during pregnancy with the microbial-derived immunomodulator OM-85 manifest striking resistance postnatally to allergic airways inflammation, and localised the potential treatment target to the fetal cDC progenitor compartment which expands to increase the pool of precursors available at birth, enabling accelerated postnatal seeding of the lung mucosal cDC network required for establishment of immunological homeostasis in the airways. Here, we profile maternal OM-85 treatment-associated transcriptomic signatures in fetal bone marrow, and identify a series of immunometabolic pathways which provide essential metabolites for accelerated myelopoiesis, that are hallmarks of classical "immune training". In addition, the cDC progenitor compartment displayed treatment-associated activation of the XBP1-ERN1 signalling axis which has previously been shown to be essential for tissue survival of cDC, particularly within the lung microenvironment. Our forerunner studies indicate uniquely rapid turnover of airway mucosal cDCs at baseline, with further large-scale upregulation of population dynamics during aeroallergen and/or pathogen challenge. XBP1-ERN1 signalling plays a key role in mitigation of ER stress-associated toxicity which frequently accompanies DC hyper-activation during intense immunoinflammatory responses, and we suggest that enhanced capacity for XBP1-ERN1-dependent cDC survival within the airway mucosal tissue microenvironment may be a crucial element of the OM-85-mediated transplacental "innate immune training" process which results in enhanced resistance to airway inflammatory disease during the high-risk early postnatal period.

immunology↗