Abstract
T-helper 2 (Th2) cell responses defend against parasites. Although dendritic cells (DCs) are vital for the induction of T-cell responses, the DC subpopulations that induce Th2 cells in the intestine are unidentified. Here we show that intestinal Th2 responses against Trichuris muris worms and Schistosoma mansoni eggs do not develop in mice with IRF-4-deficient DCs (IRF-4f/f CD11c-cre). Adoptive transfer of conventional DCs, in particular CD11b-expressing DCs from the intestine, is sufficient to prime S. mansoni-specific Th2 responses. Surprisingly, transferred IRF-4-deficient DCs also effectively prime S. mansoni-specific Th2 responses. Egg antigens do not induce the expression of IRF-4-related genes. Instead, IRF-4f/f CD11c-cre mice have fewer CD11b+ migrating DCs and fewer DCs carrying parasite antigens to the lymph nodes. Furthermore, CD11b+CD103+ DCs induce Th2 responses in the small intestine, whereas CD11b+CD103− DCs perform this role in the colon, revealing a specific functional heterogeneity among intestinal DCs in inducing Th2 responses.
Highlights
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To identify the cellular mechanisms central to the induction of T-helper 2 (Th2) responses in the intestine we developed a novel method of experimental delivery of S. mansoni eggs directly into intestinal tissue
We found that the injection of 1,000 S. mansoni eggs into the subserosal tissue of the small intestine was sufficient to induce antigen-specific Th2 and IFN-g responses in the mesenteric lymph nodes (MLN), with the key Th2 cytokines interleukin (IL)-4, IL-5 and IL-13 induced in in vitro total MLN cell cultures, after the restimulation with SEA 5 days after in vivo immunization (Fig. 1a and Supplementary Fig. 1c–e)
Summary
General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. Users may download and print one copy of any publication from the public portal for the purpose of private study or research. You may not further distribute the material or use it for any profit-making activity or commercial gain You may freely distribute the URL identifying the publication in the public portal. Different populations of CD11b þ dendritic cells drive Th2 responses in the small intestine and colon. We show that intestinal Th2 responses against Trichuris muris worms and Schistosoma mansoni eggs do not develop in mice with IRF-4-deficient DCs (IRF-4f/f CD11c-cre). Adoptive transfer of conventional DCs, in particular CD11b-expressing DCs from the intestine, is sufficient to prime S. mansoni-specific Th2 responses. Transferred IRF-4-deficient DCs effectively prime S. mansoni-specific Th2 responses. IRF-4f/f CD11c-cre mice have fewer CD11b þ migrating DCs and fewer DCs carrying parasite antigens to the lymph nodes. CD11b þ CD103 þ DCs induce Th2 responses in the small intestine, whereas CD11b þ CD103 À DCs perform this role in the colon, revealing a specific functional heterogeneity among intestinal DCs in inducing Th2 responses
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