Novel Toll-Like Receptor 9 Agonist Derived from Cryptococcus neoformans Attenuates Allergic Inflammation Leading to Asthma Onset in Mice.
Allergens
/ immunology
Animals
Asthma
/ drug therapy
Cell Differentiation
CpG Islands
/ genetics
Cryptococcus neoformans
/ metabolism
Dendritic Cells
/ immunology
Disease Models, Animal
Female
Humans
Hypersensitivity
/ drug therapy
Mice
Mice, Inbred C57BL
Oligodeoxyribonucleotides
/ genetics
Ovalbumin
/ immunology
Th1-Th2 Balance
Th2 Cells
/ immunology
Toll-Like Receptor 9
/ agonists
Asthma
Cryptococcus neoformans
Oligodeoxynucleotide
Th1
Th2
Journal
International archives of allergy and immunology
ISSN: 1423-0097
Titre abrégé: Int Arch Allergy Immunol
Pays: Switzerland
ID NLM: 9211652
Informations de publication
Date de publication:
2020
2020
Historique:
received:
31
08
2019
accepted:
22
04
2020
pubmed:
26
6
2020
medline:
2
2
2021
entrez:
26
6
2020
Statut:
ppublish
Résumé
The enhanced type 2 helper (Th2) immune response is responsible for the pathogenesis of allergic asthma. To suppress the enhanced Th2 immune response, activation of the Th1 immune response has been an alternative strategy for anti-asthma therapy. In this context, effective Th1-inducing adjuvants that inhibit the development of allergic asthma but do not flare the side effects of the primary agent are required in clinical treatment and preventive medicine. In this study, we aimed to determine the regulation of the Th2 type immune response in asthma by a novel immunostimulatory oligodeoxynucleotide (ODN) derived from Cryptococcus neoformans, termed ODN112, which contains a cytosine-guanine (CG) sequence but not canonical CpG motifs. Using an ovalbumin-induced asthma mouse model, we assessed the effect of ODN112 on prototypical asthma-related features in the lung and on the Th1/Th2 profile in the lymph nodes and lung of mice treated with ODN112 during sensitization. ODN112 treatment attenuated asthma features in mice. In the bronchial lymph nodes of the lungs and in the spleen, ODN112 increased interferon-γ production and attenuated Th2 recall responses. In dendritic cells (DCs) after allergen sensitization, ODN112 enhanced cluster of differentiation (CD) 40 and CD80 expression but did not alter CD86 expression. Interleukin-12p40 production from DCs was also increased in a Th2-polarizing condition. Our results suggest that ODN112 is a potential Th1-inducing adjuvant during Th2 cell differentiation in the sensitization phase.
Identifiants
pubmed: 32585675
pii: 000508535
doi: 10.1159/000508535
pmc: PMC7592942
doi:
Substances chimiques
Allergens
0
Oligodeoxyribonucleotides
0
Toll-Like Receptor 9
0
Ovalbumin
9006-59-1
ODN M362
ZQ12P627ZV
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
651-664Informations de copyright
© 2020 The Author(s) Published by S. Karger AG, Basel.
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