Titre
Modulation of allergic responses in mice by using biodegradable poly(lactide-co-glycolide) microspheres.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Jilek, S.
Auteure/Auteur
Walter, E.
Auteure/Auteur
Merkle, H.P.
Auteure/Auteur
Corthésy, B.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0091-6749[print], 0091-6749[linking]
Statut éditorial
Publié
Date de publication
2004
Volume
114
Numéro
4
Première page
943
Dernière page/numéro d’article
950
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
BACKGROUND: Biodegradable poly(lactide- co -glycolide) (PLGA) microspheres are a promising carrier for vaccine delivery capable of maturing antigen-presenting cells to stimulate T-cell-mediated immune responses. However, the potential of microspheres to downregulate an allergic response in vivo is unknown. OBJECTIVE: The aim of this study was to determine whether microspheres could potentiate DNA vaccination against allergy and to evaluate the immunomodulatory properties of microspheres alone. METHODS: Mice were treated prophylactically with DNA-loaded plain PLGA microspheres before sensitization with phospholipase A2 (PLA2), the major allergen of bee venom. PLA2-specific IgG1, IgG2a, IgE in serum were measured for 8.5 months, and splenocyte proliferative responses and cytokine profiles were determined. Protection against anaphylaxis was evaluated after injection of an otherwise lethal dose of PLA2. RESULTS: Phospholipase A2-specific IgG1 and IgG2a production turned out to be 2 times higher using cationic microspheres compared with anionic microspheres, but was not influenced by the presence of DNA. In contrast, reduction in IgE production and T-cell hyporesponsiveness were observed with all microsphere formulations. Recall challenge with PLA2 triggered combined expression of both IL-4 and IFN-gamma, together with sustained expression of IL-10 that can explain the protective effect against anaphylaxis. CONCLUSION: Our data suggest a dual mechanism that does initially rely on a TH2 to TH1 immune deviation and then on IL-10-mediated suppression. This is the first physiological demonstration that plain PLGA microspheres can induce tolerance in mice for as long as 6 months postsensitization.
Sujets
PID Serval
serval:BIB_C256D20180EB
PMID
Date de création
2008-01-25T13:53:13.738Z
Date de création dans IRIS
2025-05-20T21:50:03Z