Maternal prenatal immunity, neonatal trained immunity, and early airway microbiota shape childhood asthma development.
DNA methylation
childhood asthma
maternal prenatal immunity
nasal microbiome
trained innate immunity
Journal
Allergy
ISSN: 1398-9995
Titre abrégé: Allergy
Pays: Denmark
ID NLM: 7804028
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
revised:
25
05
2022
received:
28
01
2022
accepted:
11
06
2022
pubmed:
17
7
2022
medline:
1
12
2022
entrez:
16
7
2022
Statut:
ppublish
Résumé
The 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. We 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. Maternal 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. Maternal 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.
Sections du résumé
BACKGROUND
The 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.
METHODS
We 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.
RESULTS
Maternal 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.
CONCLUSIONS
Maternal 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.
Identifiants
pubmed: 35841380
doi: 10.1111/all.15442
pmc: PMC9712226
mid: NIHMS1824244
doi:
Substances chimiques
Interleukin-13
0
RNA, Ribosomal, 16S
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3617-3628Subventions
Organisme : NIEHS NIH HHS
Pays : United States
Organisme : NIH HHS
ID : R21AI133765
Pays : United States
Organisme : NIH HHS
ID : T32 ES007091
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI148104
Pays : United States
Organisme : NIH HHS
ID : R21AI144722
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI144722
Pays : United States
Organisme : NIH HHS
ID : P01AI148104
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI133765
Pays : United States
Organisme : NIH HHS
ID : R01AI042268
Pays : United States
Organisme : NIH HHS
ID : U19AI125357
Pays : United States
Informations de copyright
© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
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