Long-term alterations in lung epithelial cells after EL-RSV infection exacerbate allergic responses through IL-1β-induced pathways

Early-life (EL) respiratory infections increase pulmonary disease risk, especially EL-Respiratory Syncytial Virus (EL-RSV) infections linked to asthma. Mechanisms underlying asthma predisposition remain unknown. In this study, we examined the long-term effects on the lung after four weeks post EL-RS...

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Bibliographic Details
Published in:Mucosal immunology 2024-07
Main Authors: Morris, Susan B., Ocadiz-Ruiz, Ramon, Asai, Nobuhiro, Malinczak, Carrie-Anne, Rasky, Andrew J, Lombardo, Grace K., Velarde, Evan M., Ptaschinski, Catherine, Zemans, Rachel L, Lukacs, Nicholas W., Fonseca, Wendy
Format: Article
Language:English
Subjects:
Allergy
Asthma
IL-1β
IL-33
Lung epithelium
RSV
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Summary:Early-life (EL) respiratory infections increase pulmonary disease risk, especially EL-Respiratory Syncytial Virus (EL-RSV) infections linked to asthma. Mechanisms underlying asthma predisposition remain unknown. In this study, we examined the long-term effects on the lung after four weeks post EL-RSV infection. We identified alterations in the lung epithelial cell, with a rise in the percentage of alveolar type 2 epithelial cells (AT2) and a decreased percentage of cells in the AT1 and AT2-AT1 subclusters, as well as upregulation of Bmp2 and Krt8 genes that are associated with AT2-AT1 trans-differentiation, suggesting potential defects in lung repair processes. We identified persistent upregulation of asthma-associated genes, including Il33. EL-RSV-infected mice allergen-challenged exhibited exacerbated allergic response, with significant upregulation of Il33 in the lung and AT2 cells. Similar long-term effects were observed in mice exposed to EL-IL-1β. Notably, treatment with IL-1ra during acute EL-RSV infection mitigated the long-term alveolar alterations and the allergen-exacerbated response. Finally, epigenetic modifications in the promoter of the Il33 gene were detected in AT2 cells harvested from EL-RSV and EL-IL1β groups, suggesting that long-term alteration in the epithelium after RSV infection is dependent on the IL-1β pathway. This study provides insight into the molecular mechanisms of asthma predisposition after RSV infection.
ISSN:1933-0219
1935-3456
1935-3456
DOI:10.1016/j.mucimm.2024.07.007