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Direct interaction between cholera toxin and dendritic cells is required for oral adjuvant activity

Gustafsson, Tobias ; Hua, Yeu-Jiann ; Dahlgren, Madelene LU orcid ; Livingston, Megan ; Johansson Lindbom, Bengt LU and Yrlid, Ulf (2013) In European Journal of Immunology 43(7). p.1779-1788
Abstract
Cholera toxin (CT) binds to GM1-ganglioside receptors present on all nucleated cells. Despite this, it is a very potent mucosal adjuvant that has a dramatic impact on immune cells, as well as nerve and epithelial cells, causing diarrhea. This fact has hampered our understanding of whether the adjuvanticity of CT is direct or indirect, as cells that bind CT may or may not be involved in its adjuvant function. The mucosal barrier is maintained by tight junctions between epithelial cells but dendritic cells (DCs) can protrude luminal dendrites. Here we investigated which cells are involved in the immune augmenting effect of CT. We explored oral immunizations with ovalbumin (OVA) and CT in bone marrow chimeric mice deficient in GM1-ganglioside... (More)
Cholera toxin (CT) binds to GM1-ganglioside receptors present on all nucleated cells. Despite this, it is a very potent mucosal adjuvant that has a dramatic impact on immune cells, as well as nerve and epithelial cells, causing diarrhea. This fact has hampered our understanding of whether the adjuvanticity of CT is direct or indirect, as cells that bind CT may or may not be involved in its adjuvant function. The mucosal barrier is maintained by tight junctions between epithelial cells but dendritic cells (DCs) can protrude luminal dendrites. Here we investigated which cells are involved in the immune augmenting effect of CT. We explored oral immunizations with ovalbumin (OVA) and CT in bone marrow chimeric mice deficient in GM1-ganglioside in defined cellular subsets. We found that chimeric mice lacking GM1 in nonhematopoietic cells, including epithelial cells, mounted an unaltered intestinal IgA response. In contrast, chimeric mice lacking GM1-expressing hematopoietic cells in general, or specifically GM1-expressing conventional DCs (cDCs), largely failed to elicit anti-OVA adaptive immune responses. Therefore, the adjuvanticity of CT does not require epithelial activation, but is directly dependent on the binding of CT to gut cDCs via GM1-ganglioside. These results could have important implications for the generation of novel oral adjuvants. (Less)
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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cholera toxin, DC, IgA, Mucosal immunity, Oral adjuvants
in
European Journal of Immunology
volume
43
issue
7
pages
1779 - 1788
publisher
John Wiley & Sons Inc.
external identifiers
  • wos:000327695500013
  • scopus:84880009462
  • pmid:23649516
ISSN
1521-4141
DOI
10.1002/eji.201242867
language
English
LU publication?
yes
id
511e62d6-9a6d-4a0a-a4fe-a19132954e5e (old id 4273204)
date added to LUP
2016-04-01 11:09:10
date last changed
2024-05-06 06:00:07
@article{511e62d6-9a6d-4a0a-a4fe-a19132954e5e,
  abstract     = {{Cholera toxin (CT) binds to GM1-ganglioside receptors present on all nucleated cells. Despite this, it is a very potent mucosal adjuvant that has a dramatic impact on immune cells, as well as nerve and epithelial cells, causing diarrhea. This fact has hampered our understanding of whether the adjuvanticity of CT is direct or indirect, as cells that bind CT may or may not be involved in its adjuvant function. The mucosal barrier is maintained by tight junctions between epithelial cells but dendritic cells (DCs) can protrude luminal dendrites. Here we investigated which cells are involved in the immune augmenting effect of CT. We explored oral immunizations with ovalbumin (OVA) and CT in bone marrow chimeric mice deficient in GM1-ganglioside in defined cellular subsets. We found that chimeric mice lacking GM1 in nonhematopoietic cells, including epithelial cells, mounted an unaltered intestinal IgA response. In contrast, chimeric mice lacking GM1-expressing hematopoietic cells in general, or specifically GM1-expressing conventional DCs (cDCs), largely failed to elicit anti-OVA adaptive immune responses. Therefore, the adjuvanticity of CT does not require epithelial activation, but is directly dependent on the binding of CT to gut cDCs via GM1-ganglioside. These results could have important implications for the generation of novel oral adjuvants.}},
  author       = {{Gustafsson, Tobias and Hua, Yeu-Jiann and Dahlgren, Madelene and Livingston, Megan and Johansson Lindbom, Bengt and Yrlid, Ulf}},
  issn         = {{1521-4141}},
  keywords     = {{Cholera toxin; DC; IgA; Mucosal immunity; Oral adjuvants}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{1779--1788}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{European Journal of Immunology}},
  title        = {{Direct interaction between cholera toxin and dendritic cells is required for oral adjuvant activity}},
  url          = {{http://dx.doi.org/10.1002/eji.201242867}},
  doi          = {{10.1002/eji.201242867}},
  volume       = {{43}},
  year         = {{2013}},
}