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.
|
Authors | Dorothée Duluc, HyeMee Joo, Ling Ni, Wenjie Yin, Katherine Upchurch, Dapeng Li, Yaming Xue, Peter Klucar, Sandra Zurawski, Gerard Zurawski, SangKon Oh |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 192
Issue 12
Pg. 5776-88
(Jun 15 2014)
ISSN: 1550-6606 [Electronic] United States |
PMID | 24835401
(Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural)
|
Copyright | Copyright © 2014 by The American Association of Immunologists, Inc. |
Chemical References |
- 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
|
Topics |
- Antigens, Viral
(immunology)
- Dendritic Cells
(cytology, 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, immunology)
|