Related Experiment Video
Updated: May 4, 2026
Highly Efficient Transfection of Human THP-1 Macrophages by Nucleofection
Published on: September 2, 2014
IFN-beta increases listeriolysin O-induced membrane permeabilization and death of macrophages
Heather Zwaferink1, Silvia Stockinger, Parastoo Hazemi
1Max F. Perutz Laboratories, Vienna Biocenter, Department of Microbiology and Immunobiology, University of Vienna, Vienna, Austria.
Abstract:
Type I IFN (IFN-I) signaling is detrimental to cells and mice infected with Listeria monocytogenes. In this study, we investigate the impact of IFN-I on the activity of listeriolysin O (LLO), a pore-forming toxin and virulence protein released by L. monocytogenes. Treatment of macrophages with IFN-beta increased the ability of sublytic LLO concentrations to cause transient permeability of the plasma membrane. At higher LLO concentrations, IFN-beta enhanced the complete breakdown of membrane integrity and cell death. This activity of IFN-beta required Stat1. Perturbation of the plasma membrane by LLO resulted in activation of the p38MAPK pathway. IFN-beta pretreatment enhanced LLO-mediated signaling through this pathway, consistent with its ability to increase membrane damage. p38MAPK activation in response to LLO was independent of TLR4, a putative LLO receptor, and inhibition of p38MAPK neither enhanced nor prevented LLO-induced death. IFN-beta caused cells to express increased amounts of caspase 1 and to produce a detectable caspase 1 cleavage product after LLO treatment. Contrasting recent reports with another pore-forming toxin, this pathway did not aid cell survival as caspase 1-deficient cells were equally sensitive to lysis by LLO. Key lipogenesis enzymes were suppressed in IFN-beta-treated cells, which may exacerbate the membrane damage caused by LLO.
Insights
Type I Interferon (IFN-I) exacerbates Listeria monocytogenes infections by enhancing the cell-damaging effects of listeriolysin O (LLO). This increased membrane damage and cell death requires Stat1 and impacts lipogenesis.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Type I Interferon (IFN-I) signaling negatively impacts host defense against Listeria monocytogenes.
- Listeriolysin O (LLO) is a key pore-forming toxin secreted by L. monocytogenes, crucial for its virulence.
Purpose of the Study:
- To investigate how IFN-I signaling influences the activity of LLO, a critical Listeria virulence factor.
- To elucidate the cellular pathways and mechanisms by which IFN-I modulates LLO-induced cell damage.
Main Methods:
- Macrophage cell cultures treated with IFN-beta and varying concentrations of LLO.
- Analysis of plasma membrane permeability, cell viability, and activation of signaling pathways (Stat1, p38MAPK, caspase 1).
- Assessment of lipogenesis enzyme expression.
Main Results:
- IFN-beta treatment potentiated LLO-induced plasma membrane permeability and cell death in a Stat1-dependent manner.
- IFN-beta enhanced LLO-mediated p38MAPK pathway activation, independent of TLR4.
- IFN-beta increased caspase 1 expression, but caspase 1 deficiency did not alter LLO-induced cell lysis.
- IFN-beta suppressed key lipogenesis enzymes, potentially worsening membrane damage.
Conclusions:
- IFN-I signaling amplifies the cytotoxic effects of LLO, contributing to increased susceptibility during Listeria infections.
- The observed effects involve Stat1, p38MAPK, and caspase 1 pathways, with implications for host-pathogen interactions.
- Suppression of lipogenesis by IFN-I may represent a critical mechanism exacerbating LLO-mediated membrane damage.
More Related Videos
08:34Legionella pneumophila Outer Membrane Vesicles: Isolation and Analysis of Their Pro-inflammatory Potential on Macrophages
Published on: February 22, 2017
09:11Imaging of In Situ Interferon Gamma Production in the Mouse Spleen following Listeria monocytogenes Infection
Published on: July 16, 2019
