Journal article
IL-1β prevents ILC2 expansion, type 2 cytokine secretion, and mucus metaplasia in response to early-life rhinovirus infection in mice
Allergy (Copenhagen), Vol.75(8), pp.2005-2015
08/2020
DOI: 10.1111/all.14241
PMCID: PMC8066359
PMID: 32086822
Abstract
Early-life wheezing-associated respiratory infection with human rhinovirus (RV) is associated with asthma development. RV infection of 6-day-old immature mice causes mucous metaplasia and airway hyperresponsiveness which is associated with the expansion of IL-13-producing type 2 innate lymphoid cells (ILC2s) and dependent on IL-25 and IL-33. We examined regulation of this asthma-like phenotype by IL-1β.
Six-day-old wild-type or NRLP3-/- mice were inoculated with sham or RV-A1B. Selected mice were treated with IL-1 receptor antagonist (IL-1RA), anti-IL-1β, or recombinant IL-1β.
Rhinovirus infection induced Il25, Il33, Il4, Il5, Il13, muc5ac, and gob5 mRNA expression, ILC2 expansion, mucus metaplasia, and airway hyperresponsiveness. RV also induced lung mRNA and protein expression of pro-IL-1β and NLRP3 as well as cleavage of caspase-1 and pro-IL-1β, indicating inflammasome priming and activation. Lung macrophages were a major source of IL-1β. Inhibition of IL-1β signaling with IL-1RA, anti-IL-1β, or NLRP3 KO increased RV-induced type 2 cytokine immune responses, ILC2 number, and mucus metaplasia, while decreasing IL-17 mRNA expression. Treatment with IL-1β had the opposite effect, decreasing IL-25, IL-33, and mucous metaplasia while increasing IL-17 expression. IL-1β and IL-17 each suppressed Il25, Il33, and muc5ac mRNA expression in cultured airway epithelial cells. Finally, RV-infected 6-day-old mice showed reduced IL-1β mRNA and protein expression compared to mature mice.
Macrophage IL-1β limits type 2 inflammation and mucous metaplasia following RV infection by suppressing epithelial cell innate cytokine expression. Reduced IL-1β production in immature animals provides a mechanism permitting asthma development after early-life viral infection.
Details
- Title: Subtitle
- IL-1β prevents ILC2 expansion, type 2 cytokine secretion, and mucus metaplasia in response to early-life rhinovirus infection in mice
- Creators
- Mingyuan Han - Departments of Pediatrics, University of Michigan Medical School, Ann Arbor, MichiganTomoko Ishikawa - Departments of Pediatrics, University of Michigan Medical School, Ann Arbor, MichiganJennifer R Bermick - University of Iowa, Stead Family Department of PediatricsCharu Rajput - Departments of Pediatrics, University of Michigan Medical School, Ann Arbor, MichiganJing Lei - Departments of Pediatrics, University of Michigan Medical School, Ann Arbor, MichiganAdam M Goldsmith - Departments of Pediatrics, University of Michigan Medical School, Ann Arbor, MichiganCaitlin R Jarman - Departments of Pediatrics, University of Michigan Medical School, Ann Arbor, MichiganJulie Lee - University of Iowa, Obstetrics and GynecologyJ Kelley Bentley - Departments of Pediatrics, University of Michigan Medical School, Ann Arbor, MichiganMarc B Hershenson - Departments of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan
- Resource Type
- Journal article
- Publication Details
- Allergy (Copenhagen), Vol.75(8), pp.2005-2015
- DOI
- 10.1111/all.14241
- PMID
- 32086822
- PMCID
- PMC8066359
- NLM abbreviation
- Allergy
- ISSN
- 0105-4538
- eISSN
- 1398-9995
- Grant note
- R01 AI120526 / NIH HHS R01 AI120526 / NIAID NIH HHS
- Language
- English
- Date published
- 08/2020
- Academic Unit
- Stead Family Department of Pediatrics; Neonatology
- Record Identifier
- 9984170836802771
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