Interleukin-1 and interferon-γ orchestrate β-glucan-activated human dendritic cell programming via IκB-ζ modulation

Marco Cardone, Amiran K. Dzutsev, Hongchuan Li, Nicolas Riteau, Franca Gerosa, Kevin Shenderov, Robin Winkler-Pickett, Lisa Provezza, Elena Riboldi, Robert M. Leighty, Selinda J. Orr, Folkert Steinhagen, Mark D. Wewers, Alan Sher, Stephen K. Anderson, Romina Goldszmid, Daniel W. McVicar, Lyudmila Lyakh, Giorgio Trinchieri

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Recognition of microbial components via innate receptors including the C-type lectin receptor Dectin-1, together with the inflammatory environment, programs dendritic cells (DCs) to orchestrate the magnitude and type of adaptive immune responses. The exposure to β-glucan, a known Dectin-1 agonist and component of fungi, yeasts, and certain immune support supplements, activates DCs to induce T helper (Th)17 cells that are essential against fungal pathogens and extracellular bacteria but may trigger inflammatory pathology or autoimmune diseases. However, the exact mechanisms of DC programming by β-glucan have not yet been fully elucidated. Using a gene expression/perturbation approach, we demonstrate that in human DCs β-glucan transcriptionally activates via an interleukin (IL)-1-and inflammasome-mediated positive feedback late-induced genes that bridge innate and adaptive immunity. We report that in addition to its known ability to directly prime Tcells toward the Th17 lineage, IL-1 by promoting the transcriptional cofactor inhibitor of κB-ζ (IκB-ζ) also programs β-glucan-exposed DCs to express cell adhesion and migration mediators, antimicrobial molecules, and Th17-polarizing factors. Interferon (IFN)-γ interferes with the IL-1/IκB-ζ axis in β-glucan-activated DCs and promotes T cell-mediated immune responses with increased release of IFN-γ and IL-22, and diminished production of IL-17. Thus, our results identify IL-1 and IFN-γ as regulators of DC programming by β-glucan. These molecular networks provide new insights into the regulation of the Th17 response as well as new targets for the modulation of immune responses to β-glucan-containing microorganisms.

Original languageEnglish
Article numbere114516
JournalPLoS One
Volume9
Issue number12
DOIs
Publication statusPublished - Dec 4 2014

Fingerprint

Glucans
interleukin-1
interferons
glucans
dendritic cells
Interleukin-1
Dendritic Cells
Interferons
Modulation
Adaptive Immunity
Inflammasomes
C-Type Lectins
Th17 Cells
receptors
T-cells
Interleukin-17
autoimmune diseases
Cell adhesion
Pathology
Pathogens

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Cardone, M., Dzutsev, A. K., Li, H., Riteau, N., Gerosa, F., Shenderov, K., ... Trinchieri, G. (2014). Interleukin-1 and interferon-γ orchestrate β-glucan-activated human dendritic cell programming via IκB-ζ modulation. PLoS One, 9(12), [e114516]. https://doi.org/10.1371/journal.pone.0114516

Interleukin-1 and interferon-γ orchestrate β-glucan-activated human dendritic cell programming via IκB-ζ modulation. / Cardone, Marco; Dzutsev, Amiran K.; Li, Hongchuan; Riteau, Nicolas; Gerosa, Franca; Shenderov, Kevin; Winkler-Pickett, Robin; Provezza, Lisa; Riboldi, Elena; Leighty, Robert M.; Orr, Selinda J.; Steinhagen, Folkert; Wewers, Mark D.; Sher, Alan; Anderson, Stephen K.; Goldszmid, Romina; McVicar, Daniel W.; Lyakh, Lyudmila; Trinchieri, Giorgio.

In: PLoS One, Vol. 9, No. 12, e114516, 04.12.2014.

Research output: Contribution to journalArticle

Cardone, M, Dzutsev, AK, Li, H, Riteau, N, Gerosa, F, Shenderov, K, Winkler-Pickett, R, Provezza, L, Riboldi, E, Leighty, RM, Orr, SJ, Steinhagen, F, Wewers, MD, Sher, A, Anderson, SK, Goldszmid, R, McVicar, DW, Lyakh, L & Trinchieri, G 2014, 'Interleukin-1 and interferon-γ orchestrate β-glucan-activated human dendritic cell programming via IκB-ζ modulation', PLoS One, vol. 9, no. 12, e114516. https://doi.org/10.1371/journal.pone.0114516
Cardone, Marco ; Dzutsev, Amiran K. ; Li, Hongchuan ; Riteau, Nicolas ; Gerosa, Franca ; Shenderov, Kevin ; Winkler-Pickett, Robin ; Provezza, Lisa ; Riboldi, Elena ; Leighty, Robert M. ; Orr, Selinda J. ; Steinhagen, Folkert ; Wewers, Mark D. ; Sher, Alan ; Anderson, Stephen K. ; Goldszmid, Romina ; McVicar, Daniel W. ; Lyakh, Lyudmila ; Trinchieri, Giorgio. / Interleukin-1 and interferon-γ orchestrate β-glucan-activated human dendritic cell programming via IκB-ζ modulation. In: PLoS One. 2014 ; Vol. 9, No. 12.
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