ArticlePLoS pathogens2021
Nasal alum-adjuvanted vaccine promotes IL-33 release from alveolar epithelial cells that elicits IgA production via type 2 immune responses.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Necroptosis and the RIPK1-RIPK3-MLKL pathway in chronic kidney disease: mechanisms, crosstalk, and therapeutic opportunities.Renal failure · 2026Review
- Convergent hub pathways targeted by IAV, SARS-CoV-2, and RSV in type II alveolar epithelial cells: molecular mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- Microarray-based characterization of airway inflammation induced by environmental Acanthamoeba exposure versus the ovalbumin-alum model.Parasites, hosts and diseases · 2025Article
- Mucosal immunotherapy targeting APC in lung disease.Journal of inflammation (London, England) · 2025Review
- Calboxyvinyl polymer adjuvant enhances respiratory iga responses through mucosal and systemic administration.NPJ vaccines · 2025Article
- Importance of Vaccine Adjuvants: A Comparative Study of Antibody Acquisition Rates and Levels Before and After Adjuvant Change in the Hepatitis B Vaccine.Internal medicine (Tokyo, Japan) · 2025Article
- Intranasal influenza-vectored vaccine expressing pneumococcal surface protein A protects against Influenza and Streptococcus pneumoniae infections.NPJ vaccines · 2024Article
- Ozone as an environmental driver of influenza.Nature communications · 2024Article
- Mucosal vaccination with outer membrane vesicles derived fromFrontiers in immunology · 2024Article
- Scanning Electron Microscopy and EDX Spectroscopy of Commercial Swabs Used for COVID-19 Lateral Flow Testing.Toxics · 2023Article
- Inhibition of importin-7 attenuates ventilator-induced lung injury by targeting nuclear translocation of p38.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- Peptide Aggregation Induced Immunogenic Rupture (PAIIR).Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- ILC2s expanded by exogenous IL-33 regulate CD45+CD11b+F4/80high macrophage polarization to alleviate hepatic ischemia-reperfusion injury.Frontiers in immunology · 2022Article
- Crosstalk between ILC2s and Th2 CD4Journal of immunology research · 2022Review
- Could Interleukin-33 (IL-33) Govern the Outcome of an Equine Influenza Virus Infection? Learning from Other Species.Viruses · 2021Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aluminum hydroxide salts (alum) have been added to inactivated vaccines as safe and effective adjuvants to increase the effectiveness of vaccination. However, the exact cell types and immunological factors that initiate mucosal immune responses to alum adjuvants are unclear. In this study, the mechanism of action of alum adjuvant in nasal vaccination was investigated. Alum has been shown to act as a powerful and unique adjuvant when added to a nasal influenza split vaccine in mice. Alum is cytotoxic in the alveoli and stimulates the release of damage-associated molecular patterns, such as dsDNA, interleukin (IL)-1α, and IL-33. We found that Ag-specific IgA antibody (Ab) production was markedly reduced in IL-33-deficient mice. However, no decrease was observed in Ag-specific IgA Ab production with DNase I treatment, and no decrease was observed in IL-1α/β or IL-6 production in IL-33-deficient mice. From the experimental results of primary cultured cells and immunofluorescence staining, although IL-1α was secreted by alveolar macrophage necroptosis, IL-33 release was observed in alveolar epithelial cell necroptosis but not in alveolar macrophages. Alum- or IL-33-dependent Ag uptake enhancement and elevation of OX40L expression were not observed. By stimulating the release of IL-33, alum induced Th2 immunity via IL-5 and IL-13 production in group 2 innate lymphoid cells (ILC2s) and increased MHC class II expression in antigen-presenting cells (APCs) in the lung. Our results suggest that IL-33 secretion by epithelial cell necroptosis initiates APC- and ILC2-mediated T cell activation, which is important for the enhancement of Ag-specific IgA Ab production by alum.
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