Salmonella induces macrophage death by caspase‐1‐dependent necrosis

  title={Salmonella induces macrophage death by caspase‐1‐dependent necrosis},
  author={Molly Brennan and Brad T. Cookson},
  journal={Molecular Microbiology},
We provide evidence that Salmonella typhimurium kills phagocytes by an unusual proinflammatory mechanism of necrosis that is distinguishable from apoptosis. Infection stimulated a distinctly diffuse pattern of DNA fragmentation in macrophages, which contrasted with the marked nuclear condensation displayed by control cells undergoing chemically induced apoptosis. In apoptotic cells, DNA fragmentation and nuclear condensation result from caspase‐3‐mediated proteolysis; caspases also subvert… 

Caspase‐1‐dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages

This mechanism of caspase‐1‐mediated cell death provides additional experimental evidence supporting pyroptosis as a novel pathway of inflammatory programmed cell death.

Necrosis‐like cell death induced by bacteria in mouse macrophages

It is reported that, in addition to the apoptotic form already established, a necrosis‐like form of cell death is induced by pyogenic bacteria in mouse macrophages, and this form of necrosis may have a previously unsuspected role in the development of an immune response.

Intracytosolic Listeria monocytogenes induces cell death through caspase‐1 activation in murine macrophages

It was found that caspase‐1 activation preceded cell death of macrophages infected with L.’monocytogenes, using fluorogenic substrates, which would constitute a defence mechanism ofmacrophages which induces cell death to eliminate the bacteria's intracytosolic niche and recruits early host's defences through the secretion of inflammatory cytokines.

Caspase‐1‐induced pyroptotic cell death

The role of distinct inflammasomes, including NLRC4, NLRP3, and AIM2, as well as the role of the ASC focus in Caspase‐1 signaling are discussed, further reviewing the importance of pyroptosis in vivo as a potent mechanism to clear intracellular pathogens.

Shigella-induced necrosis and apoptosis of U937 cells and J774 macrophages.

Shigella can induce rapid necrosis of macrophage-like cells in a virulence-related manner by forming pores in the host cell membrane while some cells can be killed through apoptosis in a Virulence-independent fashion.

Salmonella pathogenicity island 2‐dependent macrophage death is mediated in part by the host cysteine protease caspase‐1

It is shown here that the human pathogen Salmonella typhi also triggers both rapid, caspase‐1‐dependent and delayed cell death in human monocytes and that IL‐1β is released during both SPI1‐ and SPI2‐dependent macrophage killing.

A Novel Caspase-1/Toll-like Receptor 4-independent Pathway of Cell Death Induced by Cytosolic Shigella in Infected Macrophages*

It is shown that Shigella infection of macrophages can also induce cell death independent of caspase-1 or IpaB activity, which identifies a novel cell death pathway induced by intracellular Gram-negative bacteria that may play a role in microbial-host interactions and inflammatory responses.

Pyroptosis and host cell death responses during Salmonella infection

Salmonella‐induced pyroptosis serves as a model to understand a broadly important pathway of proinflammatory programmed host cell death: examining this system affords insight into mechanisms of both beneficial and pathological cell death and strategies employed by pathogens to modulate host responses.

Macrophage Activation Redirects Yersinia-Infected Host Cell Death from Apoptosis to Caspase-1-Dependent Pyroptosis

Host signaling triggered by TLR and other activating ligands during the course of Yersinia infection redirects both the mechanism of host cell death and the downstream consequences of death by shifting from noninflammatory apoptosis to inflammatory pyroptosis.

Bordetella type III secretion induces caspase 1‐independent necrosis

It is concluded that the B. bronchiseptica TIII secretion system induces a mode of cell death consistent with necrosis that is distinct from that of Yersinia and Shigella.



Salmonella spp. are cytotoxic for cultured macrophages

Results indicate a close correlation between the mechanisms of bacterial internalization into non‐phagocytic cells and those that lead to macrophage cytotoxicity.

The Salmonella invasin SipB induces macrophage apoptosis by binding to caspase-1.

The data demonstrate that SipB functions as an analog of the Shigella invasin IpaB, and functional inhibition of caspase-1 activity by acetyl-Tyr-Val-Ala-Asp-chloromethyl ketone blocks macrophage cytotoxicity, and macrophages lacking casp enzyme are not susceptible to Salmonella-induced apoptosis.

Salmonella typhimurium invasion induces apoptosis in infected macrophages.

It is shown that the macrophage cytotoxicity mediated by invasive Salmonella is apoptosis, as shown by nuclear morphology, cytoplasmic vacuolization, and host cell DNA fragmentation.

Internucleosomal DNA cleavage triggered by plasma membrane damage during necrotic cell death. Involvement of serine but not cysteine proteases.

The results suggest a novel pathway of endonuclease activation during necrosis not involving the participation of caspases and indicate that techniques based on double-strand DNA breaks may not reliably differentiate between apoptosis and necrosis.

Caspase-3 Is Required for DNA Fragmentation and Morphological Changes Associated with Apoptosis*

Results indicate that although caspase-3 is not essential for TNF- or staurosporine-induced apoptosis, it is required for DNA fragmentation and some of the typical morphological changes of cells undergoing apoptosis.

Salmonella Exploits Caspase-1 to Colonize Peyer's Patches in a Murine Typhoid Model

The results show that Casp-1, which is both proapoptotic and proinflammatory, is essential for S. typhimurium to efficiently colonize the cecum and PP and subsequently cause systemic typhoid-like disease in mice.

Poly(ADP-ribose) polymerase is a mediator of necrotic cell death by ATP depletion.

  • H. HaS. Snyder
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1999
These findings, together with cell death patterns in PARP(-/-) animals receiving other types of insults, indicate that PARP activation is an active trigger of necrosis, whereas other mechanisms mediate apoptosis.

Interaction of Yersinia enterocolitica with macrophages leads to macrophage cell death through apoptosis

The data demonstrate for the first time that Y. enterocolitica promotes the apoptosis of macrophages, an effect which is clearly distinct from the morphological alterations mediated by Yersinia on epithelial HeLa cells.

Apoptosis, oncosis, and necrosis. An overview of cell death.

Some of the typical features of apoptosis are discussed, such as budding (as opposed to blebbing and zeiosis) and the inflammatory response, and stands in contrast to apoptosis, which leads to necrosis with karyorhexis and cell shrinkage.

Shigella-induced Apoptosis Is Dependent on Caspase-1 Which Binds to IpaB*

Data indicate that Shigella-induced apoptosis is distinct from other forms of apoptosis and seems uniquely dependent on Casp-1.