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Intestinal CD103+CD11b+ cDC2 conventional dendritic cells are required for primary CD4+ T and B cell responses to soluble flagellin

Flores-Langarica, Adriana ; Cook, Charlotte ; Luda, Katarzyna Müller LU ; Persson, Emma K. LU ; Marshall, Jennifer L. ; Beristain-Covarrubias, Nonantzin ; Yam-Puc, Juan Carlos ; Dahlgren, Madelene LU ; Persson, Jenny J. LU and Uematsu, Satoshi , et al. (2018) In Frontiers in Immunology 9(OCT).
Abstract

Systemic immunization with soluble flagellin (sFliC) from Salmonella Typhimurium induces mucosal responses, offering potential as an adjuvant platform for vaccines. Moreover, this engagement of mucosal immunity is necessary for optimal systemic immunity, demonstrating an interaction between these two semi-autonomous immune systems. Although TLR5 and CD103+CD11b+ cDC2 contribute to this process, the relationship between these is unclear in the early activation of CD4+ T cells and the development of antigen-specific B cell responses. In this work, we use TLR5-deficient mice and CD11c-cre.Irf4fl/fl mice (which have reduced numbers of cDC2, particularly intestinal CD103+CD11b+ cDCs), to address these points by studying the responses... (More)

Systemic immunization with soluble flagellin (sFliC) from Salmonella Typhimurium induces mucosal responses, offering potential as an adjuvant platform for vaccines. Moreover, this engagement of mucosal immunity is necessary for optimal systemic immunity, demonstrating an interaction between these two semi-autonomous immune systems. Although TLR5 and CD103+CD11b+ cDC2 contribute to this process, the relationship between these is unclear in the early activation of CD4+ T cells and the development of antigen-specific B cell responses. In this work, we use TLR5-deficient mice and CD11c-cre.Irf4fl/fl mice (which have reduced numbers of cDC2, particularly intestinal CD103+CD11b+ cDCs), to address these points by studying the responses concurrently in the spleen and the mesenteric lymph nodes (MLN). We show that CD103+CD11b+ cDC2 respond rapidly and accumulate in the MLN after immunization with sFliC in a TLR5-dependent manner. Furthermore, we identify that whilst CD103+CD11b+ cDC2 are essential for the induction of primary T and B cell responses in the mucosa, they do not play such a central role for the induction of these responses in the spleen. Additionally, we show the involvement of CD103+CD11b+ cDC2 in the induction of Th2-associated responses. CD11c-cre.Irf4fl/fl mice showed a reduced primary FliC-specific Th2-associated IgG1 responses, but enhanced Th1-associated IgG2c responses. These data expand our current understanding of the mucosal immune responses promoted by sFliC and highlights the potential of this adjuvant for vaccine usage by taking advantage of the functionality of mucosal CD103+CD11b+ cDC2.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
CDC2, Dendritic cells, Flagellin, Immune response, Mucosa
in
Frontiers in Immunology
volume
9
issue
OCT
article number
2409
publisher
Frontiers Media S. A.
external identifiers
  • pmid:30386346
  • scopus:85055143183
ISSN
1664-3224
DOI
10.3389/fimmu.2018.02409
language
English
LU publication?
yes
id
8682ee63-b65c-4ff6-b343-2b664dbb5beb
date added to LUP
2018-11-15 13:45:29
date last changed
2021-10-06 03:10:54
@article{8682ee63-b65c-4ff6-b343-2b664dbb5beb,
  abstract     = {<p>Systemic immunization with soluble flagellin (sFliC) from Salmonella Typhimurium induces mucosal responses, offering potential as an adjuvant platform for vaccines. Moreover, this engagement of mucosal immunity is necessary for optimal systemic immunity, demonstrating an interaction between these two semi-autonomous immune systems. Although TLR5 and CD103+CD11b+ cDC2 contribute to this process, the relationship between these is unclear in the early activation of CD4+ T cells and the development of antigen-specific B cell responses. In this work, we use TLR5-deficient mice and CD11c-cre.Irf4fl/fl mice (which have reduced numbers of cDC2, particularly intestinal CD103+CD11b+ cDCs), to address these points by studying the responses concurrently in the spleen and the mesenteric lymph nodes (MLN). We show that CD103+CD11b+ cDC2 respond rapidly and accumulate in the MLN after immunization with sFliC in a TLR5-dependent manner. Furthermore, we identify that whilst CD103+CD11b+ cDC2 are essential for the induction of primary T and B cell responses in the mucosa, they do not play such a central role for the induction of these responses in the spleen. Additionally, we show the involvement of CD103+CD11b+ cDC2 in the induction of Th2-associated responses. CD11c-cre.Irf4<sup>fl/fl</sup> mice showed a reduced primary FliC-specific Th2-associated IgG1 responses, but enhanced Th1-associated IgG2c responses. These data expand our current understanding of the mucosal immune responses promoted by sFliC and highlights the potential of this adjuvant for vaccine usage by taking advantage of the functionality of mucosal CD103+CD11b+ cDC2.</p>},
  author       = {Flores-Langarica, Adriana and Cook, Charlotte and Luda, Katarzyna Müller and Persson, Emma K. and Marshall, Jennifer L. and Beristain-Covarrubias, Nonantzin and Yam-Puc, Juan Carlos and Dahlgren, Madelene and Persson, Jenny J. and Uematsu, Satoshi and Akira, Shizuo and Henderson, Ian R. and Lindbom, Bengt Johansson and Agace, William and Cunningham, Adam F.},
  issn         = {1664-3224},
  language     = {eng},
  month        = {10},
  number       = {OCT},
  publisher    = {Frontiers Media S. A.},
  series       = {Frontiers in Immunology},
  title        = {Intestinal CD103<sup>+</sup>CD11b<sup>+</sup> cDC2 conventional dendritic cells are required for primary CD4<sup>+</sup> T and B cell responses to soluble flagellin},
  url          = {http://dx.doi.org/10.3389/fimmu.2018.02409},
  doi          = {10.3389/fimmu.2018.02409},
  volume       = {9},
  year         = {2018},
}