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.

Supplementary data:

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 View Item