Maternal antibiotic exposure enhances ILC2 activation in neonates via downregulation of IFN1 signaling

Haixu Xu, Xianfu Yi, Zhaohai Cui, Hui Li, Lin Zhu, Lijuan Zhang, JiaLe Chen, Xutong Fan, Pan Zhou, Mulin Jun Li, Ying Yu, Qiang Liu, Dandan Huang (), Zhi Yao () and Jie Zhou ()
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Haixu Xu: Tianjin Medical University
Xianfu Yi: Tianjin Medical University
Zhaohai Cui: Tianjin Medical University
Hui Li: Tianjin Medical University
Lin Zhu: Tianjin Medical University
Lijuan Zhang: Tianjin Medical University
JiaLe Chen: Tianjin Medical University
Xutong Fan: Tianjin Medical University
Pan Zhou: Tianjin Medical University
Mulin Jun Li: Tianjin Medical University
Ying Yu: Tianjin Medical University
Qiang Liu: Tianjin Medical University General Hospital
Dandan Huang: Tianjin Medical University
Zhi Yao: Tianjin Medical University
Jie Zhou: Tianjin Medical University

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract Microbiota have an important function in shaping and priming neonatal immunity, although the cellular and molecular mechanisms underlying these effects remain obscure. Here we report that prenatal antibiotic exposure causes significant elevation of group 2 innate lymphoid cells (ILC2s) in neonatal lungs, in both cell numbers and functionality. Downregulation of type 1 interferon signaling in ILC2s due to diminished production of microbiota-derived butyrate represents the underlying mechanism. Mice lacking butyrate receptor GPR41 (Gpr41-/-) or type 1 interferon receptor IFNAR1 (Ifnar1-/-) recapitulate the phenotype of neonatal ILC2s upon maternal antibiotic exposure. Furthermore, prenatal antibiotic exposure induces epigenetic changes in ILC2s and has a long-lasting deteriorative effect on allergic airway inflammation in adult offspring. Prenatal supplementation of butyrate ameliorates airway inflammation in adult mice born to antibiotic-exposed dams. These observations demonstrate an essential role for the microbiota in the control of type 2 innate immunity at the neonatal stage, which suggests a therapeutic window for treating asthma in early life.

Date: 2023
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DOI: 10.1038/s41467-023-43903-x

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