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Macrophage apoptosis in microbial infections
H Hilbi1, A Zychlinsky, P J Sansonetti
1Skirball Institute, Department of Microbiology, New York University School of Medicine, NY 10016, USA.
Abstract:
Upon infection with a pathogen, eukaryotic cells can undergo programmed cell death as an ultimate response. Therefore, modulation of apoptosis is often a prerequisite to establish a host-pathogen relationship. Some pathogens kill macrophages by inducing apoptosis and thus overcome the microbicidal arsenal of the phagocyte. Apoptotic macrophages, on the other hand, can elicit an inflammation by secretion of proinflammatory cytokines. Shigella flexneri, the aetiological agent of bacillary dysentery, induces apoptosis in macrophages which, in agony, specifically release mature interleukin-1 beta (IL-1 beta). This cytokine attracts neutrophils (PMN) to the site of infection resulting in the massive colonic inflammation characteristic of bacillary dysentery. Shigellosis represents a paradigm of a proinflammatory apoptosis in a bacterial infection. The molecular link between apoptosis and inflammation is interleukin-1 beta converting enzyme (ICE) which is activated during macrophage apoptosis and binds to IpaB, a secreted Shigella protein.
Insights
Shigella flexneri infection triggers programmed cell death (apoptosis) in macrophages, leading to inflammation. This process involves the release of interleukin-1 beta (IL-1 beta), a key mediator of the inflammatory response in bacillary dysentery.
Area of Science:
- Microbiology
- Immunology
- Cell Biology
Background:
- Pathogen infection often necessitates host cell apoptosis for establishing a host-pathogen relationship.
- Some pathogens induce macrophage apoptosis to evade host defenses.
- Apoptotic macrophages can secrete proinflammatory cytokines, contributing to inflammation.
Purpose of the Study:
- To elucidate the mechanism by which Shigella flexneri induces apoptosis in macrophages.
- To understand the role of apoptosis in the inflammatory response during Shigella infection.
- To identify the molecular link between apoptosis and inflammation mediated by Shigella.
Main Methods:
- Investigating the induction of apoptosis in macrophages by Shigella flexneri.
- Analyzing the secretion of mature interleukin-1 beta (IL-1 beta) from apoptotic macrophages.
- Identifying the role of interleukin-1 beta converting enzyme (ICE) and its interaction with Shigella protein IpaB.
Main Results:
- Shigella flexneri induces apoptosis in macrophages.
- Apoptotic macrophages infected with Shigella specifically release mature IL-1 beta.
- IL-1 beta secretion attracts neutrophils (PMN), causing colonic inflammation characteristic of bacillary dysentery.
- Interleukin-1 beta converting enzyme (ICE) activation during apoptosis links to IpaB, a Shigella protein.
Conclusions:
- Shigella-induced macrophage apoptosis is a proinflammatory event.
- The release of IL-1 beta from apoptotic macrophages is crucial for initiating the inflammatory cascade in Shigellosis.
- The interaction between ICE and IpaB represents a key molecular mechanism connecting bacterial infection, apoptosis, and inflammation.