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Published on: August 7, 2017
Lung microbiota promotes tolerance to allergens in neonates via PD-L1
Eva S Gollwitzer1, Sejal Saglani2, Aurélien Trompette1
1Faculty of Biology and Medicine, University of Lausanne, Service de Pneumologie, BH19.206 Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
Insights
The development of lung microbiota in early life is crucial for immune system maturation. Establishing a healthy airway microbiome prevents adult-onset allergic airway inflammation by inducing regulatory T cells.
Area of Science:
- Immunology
- Microbiology
- Respiratory Medicine
Background:
- Early life environmental exposures significantly impact long-term respiratory health.
- Neonatal immune system development is critical but poorly understood.
- The role of the lung microbiota in immune maturation is a key area of investigation.
Purpose of the Study:
- To investigate the role of lung microbiota formation in neonatal immune development.
- To understand the signals driving neonatal immune system maturation.
- To determine the impact of early-life microbiota on allergic airway inflammation.
Main Methods:
- Neonatal mice were exposed to allergens and monitored for immune responses.
- Lung microbiota composition was analyzed during the first two weeks postpartum.
- Regulatory T cell (Treg) populations and their interactions (e.g., PD-L1) were studied.
- Intervention studies involved microbial colonization absence and PD-L1 blockade.
Main Results:
- Neonatal mice exposed to allergens showed exaggerated airway inflammation and T helper 2 cell responses.
- Lung microbiota composition shifted significantly in the first two weeks postpartum.
- Microbiota changes correlated with reduced allergen responsiveness and the emergence of PD-L1-dependent Treg cells.
- Absence of microbial colonization or PD-L1 blockade led to persistent allergic airway inflammation into adulthood.
Conclusions:
- Airway microbiota formation in early life is essential for inducing regulatory T cells.
- Dysregulation of the early-life airway microbiome can lead to sustained susceptibility to allergic airway inflammation.
- Interventions targeting the early-life lung microbiota may prevent adult allergic respiratory diseases.
Abstract:
Epidemiological data point toward a critical period in early life during which environmental cues can set an individual on a trajectory toward respiratory health or disease. The neonatal immune system matures during this period, although little is known about the signals that lead to its maturation. Here we report that the formation of the lung microbiota is a key parameter in this process. Immediately following birth, neonatal mice were prone to develop exaggerated airway eosinophilia, release type 2 helper T cell cytokines and exhibit airway hyper-responsiveness following exposure to house dust mite allergens, even though their lungs harbored high numbers of natural CD4(+)Foxp3(+)CD25(+)Helios(+) regulatory T (Treg) cells. During the first 2 weeks after birth, the bacterial load in the lungs increased, and representation of the bacterial phyla shifts from a predominance of Gammaproteobacteria and Firmicutes towards Bacteroidetes. The changes in the microbiota were associated with decreased aeroallergen responsiveness and the emergence of a Helios(-) Treg cell subset that required interaction with programmed death ligand 1 (PD-L1) for development. Absence of microbial colonization(10) or blockade of PD-L1 during the first 2 weeks postpartum maintained exaggerated responsiveness to allergens through to adulthood. Adoptive transfer of Treg cells from adult mice to neonates before aeroallergen exposure ameliorated disease. Thus, formation of the airway microbiota induces regulatory cells early in life, which, when dysregulated, can lead to sustained susceptibility to allergic airway inflammation in adulthood.
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