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

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

Author information

1
Baylor Institute for Immunology Research, Dallas, TX 75204; and.
2
Baylor Institute for Immunology Research, Dallas, TX 75204; and Baylor University, Institute for Biomedical Studies, Waco, TX 76706.
3
Baylor Institute for Immunology Research, Dallas, TX 75204; and Baylor University, Institute for Biomedical Studies, Waco, TX 76706 sangkono@baylorhealth.edu.

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.

PMID:
24835401
PMCID:
PMC4048825
DOI:
10.4049/jimmunol.1301661
[Indexed for MEDLINE]
Free PMC Article

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