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

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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; Persson, Emma K.; Marshall, Jennifer L.; Beristain-Covarrubias, Nonantzin; Yam-Puc, Juan Carlos; Dahlgren, Madelene; Persson, Jenny J.; Uematsu, Satoshi; Akira, Shizuo; Henderson, Ian R.; Lindbom, Bengt Johansson; Agace, William; Cunningham, Adam F.

I: Frontiers in Immunology, Vol. 9, Nr. OCT, 2409, 17.10.2018.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Flores-Langarica, A, Cook, C, Luda, KM, Persson, EK, Marshall, JL, Beristain-Covarrubias, N, Yam-Puc, JC, Dahlgren, M, Persson, JJ, Uematsu, S, Akira, S, Henderson, IR, Lindbom, BJ, Agace, W & Cunningham, AF 2018, 'Intestinal CD103+CD11b+ cDC2 conventional dendritic cells are required for primary CD4+ T and B cell responses to soluble flagellin', Frontiers in Immunology, vol. 9, nr. OCT, 2409. https://doi.org/10.3389/fimmu.2018.02409

APA

Flores-Langarica, A., Cook, C., Luda, K. M., Persson, E. K., Marshall, J. L., Beristain-Covarrubias, N., ... Cunningham, A. F. (2018). Intestinal CD103+CD11b+ cDC2 conventional dendritic cells are required for primary CD4+ T and B cell responses to soluble flagellin. Frontiers in Immunology, 9(OCT), [2409]. https://doi.org/10.3389/fimmu.2018.02409

CBE

Flores-Langarica A, Cook C, Luda KM, Persson EK, Marshall JL, Beristain-Covarrubias N, Yam-Puc JC, Dahlgren M, Persson JJ, Uematsu S, Akira S, Henderson IR, Lindbom BJ, Agace W, Cunningham AF. 2018. Intestinal CD103+CD11b+ cDC2 conventional dendritic cells are required for primary CD4+ T and B cell responses to soluble flagellin. Frontiers in Immunology. 9(OCT). https://doi.org/10.3389/fimmu.2018.02409

MLA

Vancouver

Author

Flores-Langarica, Adriana ; Cook, Charlotte ; Luda, Katarzyna Müller ; Persson, Emma K. ; Marshall, Jennifer L. ; Beristain-Covarrubias, Nonantzin ; Yam-Puc, Juan Carlos ; Dahlgren, Madelene ; Persson, Jenny J. ; Uematsu, Satoshi ; Akira, Shizuo ; Henderson, Ian R. ; Lindbom, Bengt Johansson ; Agace, William ; Cunningham, Adam F. / Intestinal CD103+CD11b+ cDC2 conventional dendritic cells are required for primary CD4+ T and B cell responses to soluble flagellin. I: Frontiers in Immunology. 2018 ; Vol. 9, Nr. OCT.

RIS

TY - JOUR

T1 - Intestinal CD103+CD11b+ cDC2 conventional dendritic cells are required for primary CD4+ T and B cell responses to soluble flagellin

AU - Flores-Langarica, Adriana

AU - Cook, Charlotte

AU - Luda, Katarzyna Müller

AU - Persson, Emma K.

AU - Marshall, Jennifer L.

AU - Beristain-Covarrubias, Nonantzin

AU - Yam-Puc, Juan Carlos

AU - Dahlgren, Madelene

AU - Persson, Jenny J.

AU - Uematsu, Satoshi

AU - Akira, Shizuo

AU - Henderson, Ian R.

AU - Lindbom, Bengt Johansson

AU - Agace, William

AU - Cunningham, Adam F.

PY - 2018/10/17

Y1 - 2018/10/17

N2 - 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.

AB - 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.

KW - CDC2

KW - Dendritic cells

KW - Flagellin

KW - Immune response

KW - Mucosa

U2 - 10.3389/fimmu.2018.02409

DO - 10.3389/fimmu.2018.02409

M3 - Article

VL - 9

JO - Frontiers in Immunology

T2 - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

IS - OCT

M1 - 2409

ER -