Role of proapoptotic BH3-only proteins in Listeria monocytogenes infection
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Updated: Mar 22, 2026
Imaging InlC Secretion to Investigate Cellular Infection by the Bacterial Pathogen Listeria monocytogenes
Published on: September 19, 2013
Camilla Margaroli1, Susanne Oberle2,3, Christine Lavanchy1
1Department of Biochemistry CIIL, University of Lausanne, Epalinges, Switzerland.
Abstract:
The ability of pathogens to influence host cell survival is a crucial virulence factor. Listeria monocytogenes (Lm) infection is known to be associated with severe apoptosis of hepatocytes and spleen cells. This impairs host defense mechanisms and thereby facilitates the spread of intracellular pathogens. The general mechanisms of apoptosis elicited by Lm infection are understood, however, the roles of BH3-only proteins during primary Lm infection have not been examined. To explore the roles of BH3-only proteins in Lm-induced apoptosis, we studied Listeria infections in mice deficient in Bim, Bid, Noxa or double deficient in BimBid or BimNoxa. We found that BimNoxa double knockout mice were highly resistant to high-dose challenge with Listeria. Decreased bacterial burden and decreased host cell apoptosis were found in the spleens of these mice. The ability of the BH3-deficient mice to clear bacterial infection more efficiently than WT was correlated with increased concentrations of ROS, neutrophil extracellular DNA trap release and downregulation of TNF-α. Our data show a novel pathway of infection-induced apoptosis that enhances our understanding of the mechanism by which BH3-only proteins control apoptotic host cell death during Listeria infection.
Insights
BH3-only proteins like Bim and Noxa regulate apoptosis during Listeria monocytogenes infection. Deleting these proteins in mice enhances host defense, reducing bacterial spread and improving survival.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Pathogen virulence relies on manipulating host cell survival.
- Listeria monocytogenes (Lm) infection induces apoptosis in hepatocytes and spleen cells, aiding pathogen spread.
- The specific roles of BH3-only proteins in Lm-induced apoptosis remain largely unexamined.
Purpose of the Study:
- To investigate the function of BH3-only proteins (Bim, Bid, Noxa) in the host's apoptotic response to primary Listeria monocytogenes infection.
- To determine the impact of BH3-only protein deficiency on host defense mechanisms and pathogen clearance.
Main Methods:
- Listeria monocytogenes infection models were established in mice.
- Studies were conducted on mice deficient in individual BH3-only proteins (Bim, Bid, Noxa) and double-deficient mice (BimBid, BimNoxa).
- Bacterial burden, host cell apoptosis, reactive oxygen species (ROS) concentrations, neutrophil extracellular DNA trap (NET) release, and TNF-α levels were assessed.
Main Results:
- BimNoxa double knockout mice exhibited significant resistance to high-dose Listeria challenge.
- These mice displayed reduced bacterial burden and decreased apoptosis in spleen cells.
- BH3-deficient mice showed enhanced bacterial clearance, correlated with increased ROS, NET release, and reduced TNF-α.
Conclusions:
- BH3-only proteins play a critical role in regulating apoptotic host cell death during Listeria monocytogenes infection.
- Targeting BH3-only proteins represents a novel therapeutic strategy to enhance host defense against intracellular bacterial pathogens.
- This study elucidates a new pathway of infection-induced apoptosis, deepening the understanding of host-pathogen interactions.
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