1. Transplacental Innate Immune Training via Maternal Microbial Exposure: Role of XBP1-ERN1 Axis in Dendritic Cell Precursor Programming.
- Author
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Mincham KT, Jones AC, Bodinier M, Scott NM, Lauzon-Joset JF, Stumbles PA, Bosco A, Holt PG, and Strickland DH
- Subjects
- Animals, Dendritic Cells immunology, Dendritic Cells metabolism, Endoribonucleases genetics, Female, Gene Regulatory Networks, Mice, Inbred BALB C, Myeloid Progenitor Cells immunology, Myeloid Progenitor Cells metabolism, Myelopoiesis drug effects, Placenta immunology, Placenta metabolism, Pregnancy, Protein Serine-Threonine Kinases genetics, Signal Transduction, Transcriptome, Unfolded Protein Response, X-Box Binding Protein 1 genetics, Cell Extracts pharmacology, Dendritic Cells drug effects, Endoribonucleases metabolism, Immunity, Innate drug effects, Maternal-Fetal Exchange drug effects, Myeloid Progenitor Cells drug effects, Placenta drug effects, Protein Serine-Threonine Kinases metabolism, X-Box Binding Protein 1 metabolism
- Abstract
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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Mincham, Jones, Bodinier, Scott, Lauzon-Joset, Stumbles, Bosco, Holt and Strickland.)
- Published
- 2020
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