Distinct <scp>DC</scp> subsets regulate adaptive Th1 and 2 responses during <i>Trichuris muris</i> infection

Demiri, Mimoza; Müller-Luda, K; Agace, William W.; Svensson‐Frej, Marcus

doi:10.1111/pim.12458

Cited by 16 publications

(14 citation statements)

References 52 publications

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“…In mice, there is a partial association between the direction of the T helper response and IgG isotype switching and so these findings may suggest that cDC2 contribute to Th2-associated responses. An association between cDC2 and Th2 polarization has been described previously in the context of infection or in atopic asthma models ( 21 , 33 – 35 ). Moreover, we are working toward developing strategies to conjugate sFliC to different antigens and evaluate if these features that sFliC is able to promote as an adjuvant can be transferred to clinically relevant antigens.…”

Section: Discussionsupporting

confidence: 60%

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

et al. 2018

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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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Section: Discussionsupporting

confidence: 60%

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

et al. 2018

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“…CD103 + cDC are recruited to the colon in response to T. muris infection . However, these Th1‐polarizing cDC are dispensable for immunity to T. muris infection, consistent with the requirement for the induction of a protective parasite‐specific Th2‐polarized immune response. CD103 − CD11b + cDC, in contrast, are important for the induction of Th2 responses in the large intestine .…”

Section: Discussionmentioning

confidence: 55%

Increased susceptibility to oral Trichuris muris infection in the specific absence of CXCR5⁺CD11c⁺ cells

Bradford

Donaldson

Forman

et al. 2018

Parasite Immunology

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Summary Trichuris muris is a natural mouse helminth pathogen which establishes infection specifically in the caecum and proximal colon. The rapid expulsion of T. muris in resistant mouse strains is associated with the induction of a protective T helper cell type 2 (Th2)‐polarized immune response. Susceptible mouse strains, in contrast, mount an inappropriate Th1 response to T. muris infection. Expression of the chemokine CXCL13 by stromal follicular dendritic cells attracts CXCR5‐expressing cells towards the B‐cell follicles. Previous studies using a complex in vivo depletion model have suggested that CXCR5‐expressing conventional dendritic cells (cDC) help regulate the induction of Th2‐polarized responses. Here, transgenic mice with CXCR5 deficiency specifically restricted to CD11c+ cells were used to determine whether the specific absence CXCR5 on CD11c+ cells such as cDC would influence susceptibility to oral T. muris infection by affecting the Th1/Th2 balance. We show that in contrast to control mice, those which lacked CXCR5 expression on CD11c+ cells failed to clear T. muris infection and developed cytokine and antibody responses that suggested a disturbed Th1/Th2 balance with enhanced IFN‐γ expression. These data suggest an important role of CXCR5‐expressing CD11c+ cells such as cDC in immunity to oral T. muris infection.

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“…Recent research has revealed that DCs play a regulatory role in the T h 0-cell polarization to different subsets and secrete various cytokines that regulate T h 0-cell differentiation, such as T h 1, T h 2, T h 17, and T reg cells (61,62). Our results showed that double-targeting peptides are crucial for DCs to present antigen and the polarization of T h 17 and T h 1 cells in the gut, adding to the present recognizing role with IBs in the small intestine.…”

Section: Discussionmentioning

confidence: 99%

Targeting peptide‐enhanced antibody and CD11c⁺dendritic cells to inclusion bodies expressing protective antigen against ETEC in mice

Jiang

Xia

et al. 2018

FASEB j.

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Enterotoxigenic Escherichia coli (ETEC) remains a massive burden in developing countries with increasing morbidity and mortality rates; it is also an important pathogen in the farming industry and is a leading cause of bacterial diarrhea. Our previous study showed that nanometer‐sized inclusion bodies (IBs) of the fimbrial adhesin subunit protein (FaeG), mutation heat‐stable enterotoxin a (mSTa), heat‐labile enterotoxin b (LTb), and STb (nontargeting) fusion protein as an oral vaccine induced both systemic and mucosal immune responses. In this study, to enhance the protective efficacy to ETEC, we used Yersinia enterocolitica adhesive and M‐cell‐targeting peptides to analyze high‐efficiency antigen‐specific immune presentation in the gut. Here, we showed that immunization with the IBs of ETEC—FaeG‐mSTa‐LTb‐STb—induced a specific systemic and mucosal immune response in the gut, whereas the combination of both targeting peptides resulted in the highest titer, protective immune response against ETEC. A lymphocyte proliferation assay has shown that the IBs induced immunologic memory. The specific antibody of the targeting groups could effectively neutralize toxins, thereby protecting the cells of the small intestine and reducing the level of cAMP and cGMP, and the groups with double targeting showed the best effect. The most important finding was that the targeting peptides stimulate the T helper (Th) cells through Th17 and Thl and that Thl cells dominated the cellular immune response. We found that the targeting peptide could also activate CD11c+ on lymphoid dendritic cells, which processed and presented antigens to T cells through Th1‐mediated IFN‐γ and IL‐12, thereby enhancing the antibody titers. The double‐targeting peptide had a better effect on stimulating the immune cells to enhance the antibody titers.—Jiang, X., Xia, S., He, X., Ma, H., Feng, Y., Liu, Z., Wang, W., Tian, M., Chen, H., Peng, F., Wang, L., Zhao, P., Ge, J., Liu, D. Targeting peptide‐enhanced antibody and CD11c+ dendritic cells to inclusion bodies expressing protective antigen against ETEC in mice. FASEB J. 33, 2836–2847 (2019). http://www.fasebj.org

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Distinct DC subsets regulate adaptive Th1 and 2 responses during Trichuris muris infection

Cited by 16 publications

References 52 publications

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

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

Increased susceptibility to oral Trichuris muris infection in the specific absence of CXCR5⁺CD11c⁺ cells

Targeting peptide‐enhanced antibody and CD11c⁺dendritic cells to inclusion bodies expressing protective antigen against ETEC in mice

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Distinct DC subsets regulate adaptive Th1 and 2 responses during Trichuris muris infection

Cited by 16 publications

References 52 publications

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

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

Increased susceptibility to oral Trichuris muris infection in the specific absence of CXCR5+CD11c+ cells

Targeting peptide‐enhanced antibody and CD11c+dendritic cells to inclusion bodies expressing protective antigen against ETEC in mice

Contact Info

Product

Resources

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Increased susceptibility to oral Trichuris muris infection in the specific absence of CXCR5⁺CD11c⁺ cells

Targeting peptide‐enhanced antibody and CD11c⁺dendritic cells to inclusion bodies expressing protective antigen against ETEC in mice