Journal Article

Transplacental Innate Immune Training via Maternal Microbial Exposure: Role of XBP1-ERN1 Axis in Dendritic Cell Precursor Programming

Strickland, Deborah, The University of Western Australia (UWA), Holt, Patrick, Bodinier, Marie, Bosco, Anthony, Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA) ; Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Mincham, Kyle, National Health and Medical Research Council of Australia :APP1047212, Centre de recherche du CHU de Québec-Université Laval (CRCHUQ) ; CHU de Québec–Université Laval ; Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Murdoch University [Perth], Lauzon-Joset, Jean-Francois, Jones, Anya, Scott, Naomi, Stumbles, Philip, The University of Queensland (UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations])

2020

Overview

We recently reported that offspring of mice treated during pregnancy with the microbial-derived immunomodulator OM-85 manifest striking resistance to allergic airways inflammation, and localized the potential treatment target to fetal conventional dendritic cell (cDC) progenitors. 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. Additionally, the cDC progenitor compartment displayed treatment-associated activation of the XBP1-ERN1 signalling axis which has been shown to be crucial for tissue survival of cDC, particularly within the lungs. 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. We suggest that enhanced capacity for XBP1-ERN1-dependent cDC survival within the airway mucosal tissue microenvironment may be a crucial element of OM-85-mediated transplacental innate immune training which results in postnatal resistance to airway inflammatory disease.

• Publisher: CCSD,Frontiers,Frontiers Media SA,Frontiers Media S.A
• Subject: Animals / Bioengineering / Bone marrow / Cell Extracts - pharmacology / Cloning / dendritic cell / Dendritic cells / Dendritic Cells - drug effects / Dendritic Cells - immunology / Dendritic Cells - metabolism / Disease resistance / Endoribonucleases - genetics / Endoribonucleases - metabolism / Female / Fetuses / Flow cytometry / Gene Regulatory Networks / Immunity, Innate - drug effects / Immunology / Immunomodulation / immunomodulator / Infectious diseases / Inflammatory diseases / innate immune training / Innate immunity / Life Sciences / Mann-Whitney U test / Maternal-Fetal Exchange - drug effects / Mice, Inbred BALB C / Microenvironments / Mothers / Mucosa / Myeloid Progenitor Cells - drug effects / Myeloid Progenitor Cells - immunology / Myeloid Progenitor Cells - metabolism / Myelopoiesis / Myelopoiesis - drug effects / Pathogens / Placenta - drug effects / Placenta - immunology / Placenta - metabolism / Population dynamics / Postpartum period / Pregnancy / Prenatal development / Progenitor cells / Protein Serine-Threonine Kinases - genetics / Protein Serine-Threonine Kinases - metabolism / Respiratory tract diseases / Signal Transduction / Software / Statistical significance / Streptococcus infections / Transcriptome / Transcriptomics / transplacental / Unfolded Protein Response / X-Box Binding Protein 1 - genetics / X-Box Binding Protein 1 - metabolism / XBP1
• ISBN: 0005988402000