Caspase-1 Activation in Macrophages Infected with
            <i>Yersinia pestis</i>
            KIM Requires the Type III Secretion System Effector YopJ

Lilo, Sarit; Zheng, Ying; Bliska, James B.

doi:10.1128/iai.01695-07

Cited by 73 publications

(110 citation statements)

References 59 publications

Supporting

Mentioning

106

Contrasting

Order By: Relevance

“…S1C) (24). Although caspase-1 is activated by Y. pestis (1,25), macrophage death was independent of caspase-1/caspase-11, suggesting nonpyroptotic cytotoxicity ( Fig. S2 A and B).…”

Section: Significancementioning

confidence: 99%

See 1 more Smart Citation

Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death

Weng

Marty-Roix

Ganesan

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

266

263

View full text Add to dashboard Cite

A number of pathogens cause host cell death upon infection, and Yersinia pestis, infamous for its role in large pandemics such as the "Black Death" in medieval Europe, induces considerable cytotoxicity. The rapid killing of macrophages induced by Y. pestis, dependent upon type III secretion system effector Yersinia outer protein J (YopJ), is minimally affected by the absence of caspase-1, caspase-11, Fas ligand, and TNF. Caspase-8 is known to mediate apoptotic death in response to infection with several viruses and to regulate programmed necrosis (necroptosis), but its role in bacterially induced cell death is poorly understood. Here we provide genetic evidence for a receptor-interacting protein (RIP) kinasecaspase-8-dependent macrophage apoptotic death pathway after infection with Y. pestis, influenced by Toll-like receptor 4-TIR-domain-containing adapter-inducing interferon-β (TLR4-TRIF). Interestingly, macrophages lacking either RIP1, or caspase-8 and RIP3, also had reduced infection-induced production of IL-1β, IL-18, TNF, and IL-6; impaired activation of the transcription factor NF-κB; and greatly compromised caspase-1 processing. Cleavage of the proform of caspase-1 is associated with triggering inflammasome activity, which leads to the maturation of IL-1β and IL-18, cytokines important to host responses against Y. pestis and many other infectious agents. Our results identify a RIP1-caspase-8/RIP3-dependent caspase-1 activation pathway after Y. pestis challenge. Mice defective in caspase-8 and RIP3 were also highly susceptible to infection and displayed reduced proinflammatory cytokines and myeloid cell death. We propose that caspase-8 and the RIP kinases are key regulators of macrophage cell death, NF-κB and inflammasome activation, and host resistance after Y. pestis infection.

show abstract

“…S1C) (24). Although caspase-1 is activated by Y. pestis (1,25), macrophage death was independent of caspase-1/caspase-11, suggesting nonpyroptotic cytotoxicity ( Fig. S2 A and B).…”

Section: Significancementioning

confidence: 99%

“…T he causative agent of plague, Yersinia pestis is well known to cause significant cell death upon infection (1)(2)(3). Like the activation of inflammatory pathways to produce cytokines, triggering cell death pathways is a common response of the mammalian immune system to infection.…”

mentioning

confidence: 99%

Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death

Weng

Marty-Roix

Ganesan

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

266

263

View full text Add to dashboard Cite

show abstract

“…To further analyze the underlying mechanism of the different courses of cell death in caspase-1 Ϫ/Ϫ and WT BMM, we determined caspase-1 and caspase-3 activation after B. pseudomallei infection. It has previously been shown that caspase-1 activation is crucial for sufficient IL-1␤ release of macrophages infected with various pathogens (25,28,41). Therefore, we examined whether caspase-1-dependent IL-1␤ release might occur in B. pseudomallei-infected BMM.…”

Section: C57bl/6 Caspase-1mentioning

confidence: 99%

Caspase-1 Mediates Resistance in Murine Melioidosis

et al. 2009

View full text Add to dashboard Cite

The gram-negative rod Burkholderia pseudomallei is the causative agent of melioidosis, a potentially fatal disease which is endemic in tropical and subtropical areas. The bacterium multiplies intracellularly within the cytosol, induces the formation of actin tails, and can spread directly from cell to cell. Recently, it has been shown that B. pseudomallei can induce caspase-1-dependent cell death in macrophages. The aim of the present study was to further elucidate the role of caspase-1 during B. pseudomallei infection. In vivo experiments with caspase-1 ؊/؊ mice revealed a high susceptibility to B. pseudomallei challenge. This phenotype was associated with a significantly higher bacterial burden 2 days after infection and decreased gamma interferon (IFN-␥) and interleukin-18 cytokine levels 24 h after infection compared to control animals. caspase-1 ؊/؊ bone marrowderived macrophages (BMM) exhibited strong caspase-3 expression and reduced cell damage compared to wild-type (WT) cells during early B. pseudomallei infection, indicating "classical" apoptosis, whereas WT BMM showed signs of rapid caspase-1-dependent cell death. Moreover, we found that caspase-1 ؊/؊ BMM had a strongly increased bacterial burden compared to WT cells 3 h after infection under conditions where no difference in cell death could be observed between both cell populations at this time point. We therefore suggest that caspase-1-dependent rapid cell death might contribute to resistance by reducing the intracellular niche for B. pseudomallei, but, in addition, caspase-1 might also have a role in controlling intracellular replication of B. pseudomallei in macrophages. Moreover, caspase-1-dependent IFN-␥ production is likely to contribute to resistance in murine melioidosis.Burkholderia pseudomallei is a gram-negative rod and the causative agent of melioidosis, an infectious disease of humans and animals in certain areas of the tropics (36). In areas of endemicity, B. pseudomallei is known to be a major cause of morbidity and mortality, and clinical manifestations are extremely variable, ranging from nonapparent to localized subacute or chronic infections and fulminant septicemias with abscesses in multiple organs (24). The infection is acquired by percutaneous inoculation, ingestion, or inhalation after contact with contaminated water, soil, or aerosols (8, 37). Underlying diseases such as diabetes and renal failure are known risk factors for an acute and fulminant course of infection (36), but the underlying immunological mechanisms responsible for the variable outcomes after B. pseudomallei infection are still unclear (6, 9, 37).B. pseudomallei is able to invade, survive, and replicate inside phagocytic and nonphagocytic cells and furthermore induces the formation of actin tails, which enable the bacterium to spread directly from cell to cell (4,18,19). Several studies have shown that gamma interferon (IFN-␥) is essential for the early control of B. pseudomallei infection in mice (3,14,31). Recently, we provided evidence for an essential role...

show abstract

“…This inhibitor has been shown to inhibit caspase-1-dependent functions in pathogens like Salmonella, Shigella, and Yersinia spp. (33,44,55). Accordingly, in the presence of Ac-YVAD-CMK, PECs infected with F. tularensis subsp.…”

Section: Vol 79 2011mentioning

confidence: 99%

IglG and IglI of the Francisella Pathogenicity Island Are Important Virulence Determinants of Francisella tularensis LVS

et al. 2011

View full text Add to dashboard Cite

The Gram-negative bacterium Francisella tularensis is the causative agent of tularemia, a disease intimately associated with the multiplication of the bacterium within host macrophages. This in turn requires the expression of Francisella pathogenicity island (FPI) genes, believed to encode a type VI secretion system. While the exact functions of many of the components have yet to be revealed, some have been found to contribute to the ability of Francisella to cause systemic infection in mice as well as to prevent phagolysosomal fusion and facilitate escape into the host cytosol. Upon reaching this compartment, the bacterium rapidly multiplies, inhibits activation of the inflammasome, and ultimately causes apoptosis of the host cell. In this study, we analyzed the contribution of the FPI-encoded proteins IglG, IglI, and PdpE to the aforementioned processes in F. tularensis LVS. The ⌬pdpE mutant behaved similarly to the parental strain in all investigated assays. In contrast, ⌬iglG and ⌬iglI mutants, although they were efficiently replicating in J774A.1 cells, both exhibited delayed phagosomal escape, conferred a delayed activation of the inflammasome, and exhibited reduced cytopathogenicity as well as marked attenuation in the mouse model. Thus, IglG and IglI play key roles for modulation of the intracellular host response and also for the virulence of F. tularensis.

show abstract

Caspase-1 Activation in Macrophages Infected with Yersinia pestis KIM Requires the Type III Secretion System Effector YopJ

Cited by 73 publications

References 59 publications

Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death

Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death

Caspase-1 Mediates Resistance in Murine Melioidosis

IglG and IglI of the Francisella Pathogenicity Island Are Important Virulence Determinants of Francisella tularensis LVS

Contact Info

Product

Resources

About