Intestinal CD103+CD11b+ cDC2 Conventional Dendritic Cells Are Required for Primary CD4+ T and B Cell Responses to Soluble Flagellin

• Published in: Frontiers in immunology Vol. 9; no. OCT; p. 2409
• Main Authors: Flores-Langarica, Adriana, Cook, Charlotte, Müller Luda, Katarzyna, 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.
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 17.10.2018
• Subjects: Animals; Antigens, CD - metabolism; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Basic Medicine; CD11c Antigen - metabolism; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; cDC2; dendritic cells; Dendritic Cells - metabolism; flagellin; Flagellin - immunology; Fluorescent Antibody Technique; immune response; Immunization; Immunohistochemistry; Immunologi inom det medicinska området (Här ingår: Cell- och immunterapi); Immunology; Immunology in the Medical Area (including Cell and Immunotherapy); Integrin alpha Chains - metabolism; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Mice; Mice, Knockout; mucosa; Toll-Like Receptor 5 - metabolism; flagellin; dendritic cells; immune response; mucosa; cDC2
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2018.02409

Systemic immunization with soluble flagellin (sFliC) from 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 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. 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.