Induction and activation of human Th17 by targeting antigens to dendritic cells via Dectin-1

Dorothée Duluc, Hyemee Joo, Ling Ni, Wenjie Yin, Katherine Upchurch, Dapeng Li, Yaming Xue, Peter Klucar, Sandra Zurawski, Gerard Zurawski, Sang Kon Oh

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Recent compelling evidence indicates that Th17 confer host immunity against a variety of microbes, including extracellular and intracellular pathogens. Therefore, understanding mechanisms for the induction and activation of Ag-specific Th17 is important for the rational design of vaccines against pathogens. To study this, we employed an in vitro system in which influenza hemagglutinin (HA) 1 was delivered to dendritic cells (DCs) via Dectin-1 using anti-human Dectin-1 (hDectin-1)-HA1 recombinant fusion proteins.We found that healthy individuals maintained broad ranges of HA1-specific memory Th17 that were efficiently activated by DCs targeted with anti-hDectin-1-HA1. Nonetheless, these DCs were not able to induce a significant level of HA1-specific Th17 responses even in the presence of the Th17-promoting cytokines IL-1β and IL-6. We further found that the induction of surface IL-1R1 expression by signals via TCRs and common γ-chain receptors was essential for naive CD4+ T cell differentiation into HA1-specific Th17. This process was dependent on MyD88, but not IL-1R-associated kinase 1/4. Thus, interruptions in STAT3 or MyD88 signaling led to substantially diminished HA1-specific Th17 induction. Taken together, the de novo generation of pathogen-specific human Th17 requires complex, but complementary, actions of multiple signals. Data from this study will help us design a new and effective vaccine strategy that can promote Th17-mediated immunity against microbial pathogens.

Original languageEnglish (US)
Pages (from-to)5776-5788
Number of pages13
JournalJournal of Immunology
Volume192
Issue number12
DOIs
StatePublished - Jun 15 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Duluc, D., Joo, H., Ni, L., Yin, W., Upchurch, K., Li, D., Xue, Y., Klucar, P., Zurawski, S., Zurawski, G., & Oh, S. K. (2014). Induction and activation of human Th17 by targeting antigens to dendritic cells via Dectin-1. Journal of Immunology, 192(12), 5776-5788. https://doi.org/10.4049/jimmunol.1301661