OceanRep
Nod2-mediated recognition of the microbiota is critical for mucosal adjuvant activity of cholera toxin.
Kim, D., Kim, Y. G., Seo, S. U., Kim, D. J., Kamada, N., Prescott, D., Philpott, D. J., Rosenstiel, Philip, Inohara, N. and Nunez, G. (2016) Nod2-mediated recognition of the microbiota is critical for mucosal adjuvant activity of cholera toxin. Nature Medicine, 22 (5). pp. 524-530. DOI 10.1038/nm.4075.
Full text not available from this repository.Abstract
Cholera toxin (CT) is a potent adjuvant for inducing mucosal immune responses. However, the mechanism by which CT induces adjuvant activity remains unclear. Here we show that the microbiota is critical for inducing antigen-specific IgG production after intranasal immunization. After mucosal vaccination with CT, both antibiotic-treated and germ-free (GF) mice had reduced amounts of antigen-specific IgG, smaller recall-stimulated cytokine responses, impaired follicular helper T (T-FH) cell responses and reduced numbers of plasma cells. Recognition of symbiotic bacteria via the nucleotide-binding oligomerization domain containing 2 (Nod2) sensor in cells that express the integrin CD11c (encoded by ltgax) was required for the adjuvanticity of CT. Reconstitution of GF mice with a Nod2 agonist or monocolonization with Staphylococcus sciuri, which has high Nod2-stimulatory activity, was sufficient to promote robust CT adjuvant activity, whereas bacteria with low Nod2-stimulatory activity did not. Mechanistically, CT enhanced Nod2-mediated cytokine production in dendritic cells via intracellular cyclic AMP. These results show a role for the microbiota and the intracellular receptor Nod2 in promoting the mucosal adjuvant activity of CT.
Document Type: | Article |
---|---|
Additional Information: | Times Cited: 3 Kim, Donghyun Kim, Yun-Gi Seo, Sang-Uk Kim, Dong-Jae Kamada, Nobuhiko Prescott, Dave Philpott, Dana J. Rosenstiel, Philip Inohara, Naohiro Nunez, Gabriel |
Keywords: | Immunology, Vaccines |
Research affiliation: | Kiel University > Kiel Marine Science OceanRep > The Future Ocean - Cluster of Excellence Kiel University |
Refereed: | Yes |
Open Access Journal?: | No |
Publisher: | Nature Research |
Projects: | Future Ocean |
Date Deposited: | 14 Mar 2017 15:17 |
Last Modified: | 27 May 2019 10:28 |
URI: | https://oceanrep.geomar.de/id/eprint/36163 |
Actions (login required)
View Item |
Copyright 2023 | GEOMAR Helmholtz-Zentrum für Ozeanforschung Kiel | All rights reserved
Questions, comments and suggestions regarding the GEOMAR repository are welcomed
at bibliotheksleitung@geomar.de !