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

J Immunol. 2014 Jun 15;192(12):5776-88. doi: 10.4049/jimmunol.1301661. Epub 2014 May 16.


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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigens, Viral / immunology*
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Female
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Humans
  • Interleukin-1beta / immunology
  • Interleukin-6 / immunology
  • Lectins, C-Type / immunology*
  • Male
  • Myeloid Differentiation Factor 88 / immunology
  • Th17 Cells / cytology
  • Th17 Cells / immunology*


  • Antigens, Viral
  • CLEC7A protein, human
  • H1N1 virus hemagglutinin
  • Hemagglutinin Glycoproteins, Influenza Virus
  • IL1B protein, human
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-6
  • Lectins, C-Type
  • MYD88 protein, human
  • Myeloid Differentiation Factor 88