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

Area of Science:

• Immunology
• Cell Biology
• Microbiology

Background:

• Dendritic cells (DCs) are crucial for adaptive immunity, programmed by innate receptors like Dectin-1.
• Beta-glucan, a Dectin-1 agonist, activates DCs to induce T helper 17 (Th17) cells, important for fungal and bacterial defense but potentially linked to inflammation.

Purpose of the Study:

• To elucidate the precise mechanisms of DC programming by beta-glucan.
• To identify molecular regulators of DC responses to beta-glucan.

Main Methods:

• Gene expression analysis and perturbation in human DCs exposed to beta-glucan.
• Investigation of the roles of IL-1, inflammasomes, inhibitor of κB-ζ (IκB-ζ), and IFN-γ.

Main Results:

• Beta-glucan induces late-acting genes in DCs via an IL-1 and inflammasome-mediated positive feedback loop.
• IL-1 promotes IκB-ζ, leading to DC expression of adhesion molecules, antimicrobials, and Th17-polarizing factors.
• IFN-γ counteracts the IL-1/IκB-ζ axis, shifting T cell responses towards IFN-γ and IL-22 production while reducing IL-17.

Conclusions:

• IL-1 and IFN-γ are key regulators of DC programming by beta-glucan.
• These findings reveal molecular networks governing Th17 responses and suggest targets for modulating immune responses to beta-glucan-containing microbes.