Microbiota, Epigenetics, and Trained Immunity. Convergent Drivers and Mediators of the Asthma Trajectory from Pregnancy to Childhood.
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ABSTRACT:
SUBMITTER: Lynch SV
PROVIDER: S-EPMC8017579 | biostudies-literature | 2021 Apr
REPOSITORIES: biostudies-literature
Publications
Microbiota, Epigenetics, and Trained Immunity. Convergent Drivers and Mediators of the Asthma Trajectory from Pregnancy to Childhood.
Lynch Susan V SV Vercelli Donata D
American journal of respiratory and critical care medicine 20210401 7
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Project description:SignificanceA growing body of clinical and experimental evidence has challenged the traditional understanding that only the adaptive immune system can mount immunological memory. Recent findings describe the adaptive characteristics of the innate immune system, underscored by its ability to remember antecedent foreign encounters and respond in a nonspecific sensitized manner to reinfection. This has been termed trained innate immunity. Although beneficial in the context of recurrent infections, this might actually contribute to chronic immune-mediated diseases, such as atherosclerosis. Recent Advances: In line with its proposed role in sustaining cellular memories, epigenetic reprogramming has emerged as a critical determinant of trained immunity. Recent technological and computational advances that improve unbiased acquisition of epigenomic profiles have significantly enhanced our appreciation for the complexities of chromatin architecture in the contexts of diverse immunological challenges.Critical issuesKey to resolving the distinct chromatin signatures of innate immune memory is a comprehensive understanding of the precise physiological targets of regulatory proteins that recognize, deposit, and remove chemical modifications from chromatin as well as other gene-regulating factors. Drawing from a rapidly expanding compendium of experimental and clinical studies, this review details a current perspective of the epigenetic pathways that support the adapted phenotypes of monocytes and macrophages.Future directionsWe explore future strategies that are aimed at exploiting the mechanism of trained immunity to improve the prevention and treatment of infections and immune-mediated chronic disorders.
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Project description:BackgroundThe path to childhood asthma is thought to initiate in utero and be further promoted by postnatal exposures. However, the underlying mechanisms remain underexplored. We hypothesized that prenatal maternal immune dysfunction associated with increased childhood asthma risk (revealed by low IFN-γ:IL-13 secretion during the third trimester of pregnancy) alters neonatal immune training through epigenetic mechanisms and promotes early-life airway colonization by asthmagenic microbiota.MethodsWe examined epigenetic, immunologic, and microbial features potentially related to maternal prenatal immunity (IFN-γ:IL-13 ratio) and childhood asthma in a birth cohort of mother-child dyads sampled pre-, peri-, and postnatally (N = 155). Epigenome-wide DNA methylation and cytokine production were assessed in cord blood mononuclear cells (CBMC) by array profiling and ELISA, respectively. Nasopharyngeal microbiome composition was characterized at age 2-36 months by 16S rRNA sequencing.ResultsMaternal prenatal immune status related to methylome profiles in neonates born to non-asthmatic mothers. A module of differentially methylated CpG sites enriched for microbe-responsive elements was associated with childhood asthma. In vitro responsiveness to microbial products was impaired in CBMCs from neonates born to mothers with the lowest IFN-γ:IL-13 ratio, suggesting defective neonatal innate immunity in those who developed asthma during childhood. These infants exhibited a distinct pattern of upper airway microbiota development characterized by early-life colonization by Haemophilus that transitioned to a Moraxella-dominated microbiota by age 36 months.ConclusionsMaternal prenatal immune status shapes asthma development in her child by altering the epigenome and trained innate immunity at birth, and is associated with pathologic upper airway microbial colonization in early life.
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
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