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Publication
Recognition of the microbiota by Nod2 contributes to the oral adjuvant activity
of cholera toxin through the induction of interleukin-1ß.
Authors Kim D, Kim YM, Kim WU, Park JH, Núñez G, Seo SU
Submitted By Submitted Externally on 4/30/2020
Status Published
Journal Immunology
Year 2019
Date Published 11/1/2019
Volume : Pages 158 : 219 - 229
PubMed Reference 31478196
Abstract The role of symbiotic bacteria in the development of antigen-specific immunity
remains poorly understood. Previous studies showed that sensing of symbiotic
bacteria by nucleotide-binding oligomerization domain-containing protein 2
(Nod2) regulates antibody responses in response to nasal immunization with
antigen and cholera toxin (CT). In this study, we examined the role of the
microbiota in the adjuvant activity of CT induced after oral immunization with
antigen. Germ-free (GF) mice showed impaired production of antibody responses
and T-cell-specific cytokines after oral immunization when compared with that
observed in conventionally raised mice. Similar to GF mice, Nod2-deficient mice
showed reduced humoral responses upon oral immunization with antigen and CT.
Treatment with CT enhanced the production of interleukin-1ß (IL-1ß), but not
tumor necrosis factor-a or IL-12p40, induced by stimulation of dendritic cells
with muramyl dipeptide, the Nod2 ligand. Mechanistically, the enhanced
production of IL-1ß induced by muramyl dipeptide and CT stimulation required
Nod2 and was mediated by both increased synthesis of pro-IL-1ß and caspase-1
activation. Furthermore, antigen-specific antibody and cytokine responses
induced by CT were impaired in orally immunized IL-1ß-deficient mice.
Collectively, our results indicate that Nod2 stimulation by symbiotic bacteria
contributes to optimal CT-mediated antigen-specific oral vaccination through the
induction of IL-1ß production.




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