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Updated: Jun 1, 2026

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
09:04

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells

Published on: May 22, 2014

Polyene macrolide antifungal drugs trigger interleukin-1β secretion by activating the NLRP3 inflammasome

Murthy Narayana Darisipudi1, Ramanjaneyulu Allam, Khader Valli Rupanagudi

  • 1Medizinische Poliklinik, University of Munich, Munich, Germany.

Plos One
|June 1, 2011
PubMed

Insights

Polyene antifungal drugs like amphotericin B, nystatin, and natamycin directly activate the host

Area of Science:

  • Immunology
  • Pharmacology
  • Mycology

Background:

  • Antimycotic drugs primarily target fungal growth.
  • Some antifungals, like amphotericin B and nystatin, can trigger interleukin-1β (IL-1β) secretion, but the mechanism is unclear.
  • The innate immune response plays a crucial role in host defense against fungal infections.

Purpose of the Study:

  • To investigate the molecular mechanism by which polyene macrolide antifungal drugs induce IL-1β secretion.
  • To determine if other classes of antifungals also trigger IL-1β secretion.
  • To elucidate the role of inflammasomes and specific cellular pathways in this immune activation.

Main Methods:

  • In-vitro stimulation of dendritic cells from C57BL/6 mouse bone marrow with polyene macrolides (amphotericin B, nystatin, natamycin) and azole antifungals.
  • Assessment of IL-1β secretion and its dependence on Toll-like receptor (TLR) signaling, NLRP3 inflammasome components (ASC, caspase-1), and potassium efflux.
  • Investigation of the role of P2X7 receptor and phagocytosis in natamycin-induced IL-1β release.

Main Results:

  • Polyene macrolides (amphotericin B, nystatin, natamycin) but not azoles induced significant IL-1β secretion in dendritic cells.
  • IL-1β release was dependent on TLR-mediated pro-IL-1β induction and activation of the NLRP3 inflammasome, ASC, and caspase-1.
  • Potassium efflux was induced by all three polyene drugs, activating NLRP3, but P2X7 receptor was not required.
  • Natamycin-induced IL-1β secretion involved phagocytosis and cathepsin activation.

Conclusions:

  • Polyene macrolide antifungal drugs directly activate the host's innate immune system.
  • This activation occurs via potassium efflux, leading to NLRP3 inflammasome assembly and IL-1β maturation and release.
  • These findings reveal a dual mechanism of action for polyene antifungals: direct fungal inhibition and host immune modulation.

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