Staying alive: bacterial inhibition of apoptosis during infection

Faherty, Christina S.; Maurelli, Anthony T.

doi:10.1016/j.tim.2008.02.001

Cited by 132 publications

(112 citation statements)

References 64 publications

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“…In mammals, apoptosis can be efficiently blocked by several pathogens via inhibition of apoptotic caspases, prevention of cytochrome c release or activation of pro-survival pathways. 53 Necroptosis has been shown to be inhibited by viral inhibitors during infection 51 and pyroptosis can be blocked through caspase-1 inhibition by pathogenic bacteria and viruses. 32 In some instances, suppression of pyroptosis by a pathogen leads to activation of autophagy, 54,55 highlighting the complex circuitry involved in cell death processes leading to pathogen clearance.…”

Section: Pathogen Strategies To Evade Cell Deathmentioning

confidence: 99%

Programmed cell death in the plant immune system

2011

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Cell death has a central role in innate immune responses in both plants and animals. Besides sharing striking convergences and similarities in the overall evolutionary organization of their innate immune systems, both plants and animals can respond to infection and pathogen recognition with programmed cell death. The fact that plant and animal pathogens have evolved strategies to subvert specific cell death modalities emphasizes the essential role of cell death during immune responses. The hypersensitive response (HR) cell death in plants displays morphological features, molecular architectures and mechanisms reminiscent of different inflammatory cell death types in animals (pyroptosis and necroptosis). In this review, we describe the molecular pathways leading to cell death during innate immune responses. Additionally, we present recently discovered caspase and caspase-like networks regulating cell death that have revealed fascinating analogies between cell death control across both kingdoms.

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Section: Pathogen Strategies To Evade Cell Deathmentioning

confidence: 99%

Programmed cell death in the plant immune system

2011

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“…Therefore, p21 shows both anticancer and procancer properties. Among the anti-apoptotic genes activated by NF-κB, transcripts for inhibitor of apoptosis proteins (IAPs) are rapidly induced in response to LPS and delay apoptosis through direct and indirect inhibition of caspase activity (27,28). IAPs are a novel family of proteins that are thought to inhibit cell death via direct inhibition of caspases (29).…”

Section: Inhibition Of Egr-1 By Sirna In Prostate Carcinoma Cell Linementioning

confidence: 99%

Inhibition of Egr-1 by siRNA in prostate carcinoma cell lines is associated with decreased expression of AP-1 and NF-κB

Parra

Ferreira²,

Sáenz³

2011

Int J Mol Med

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Abstract. Previous studies suggest that the effects of Egr-1 on tumorigenesis are critically dependent on the levels of Egr-1 and the cellular context. For this reason, we examined the effects of blocking the Egr-1 activity by a short interfering RNA (siRNA) against Egr-1 on the expression of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) signaling in the PC-3 and LNCaP prostate carcinoma cell lines. We observed that the reduction in expression of Egr-1 in PC-3 and LNCaP cells by effects of the siRNA vector resulted in lower cell viability and increased apoptosis at 24 and 120 h after transfection. This reduced cell viability correlated well with a reduced activity of the NF-κB and AP-1 factors. We analyzed the expression and activity of these factors and found that p65 and IκB but not p50 were reduced in the siRNA-treated cells. Similarly, we found that c-Fos but not c-Jun was reduced in the siRNA treated cells. These effects were translated to reduced transcriptional activity of NF-κB over cellular inhibitor of apoptosis (cIAP) and p21 genes, as assayed by RT-PCR and of AP-1 over a luciferase reporter activated by AP-1 response elements. Egr-1 was also found to interact directly with p65 and IκB members of the NF-κB family, thereby was able to regulate directly their activity by post-transcriptional effects. These results suggest that Egr-1 may promote prostate cancer development by modulating the activity of factors NF-κB and AP-1, which are involved in cell proliferation and apoptosis.

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“…5 Exploiting AKT pathway to inhibit host cell apoptosis has also been documented during infection with Salmonella, Anaplasma, Toxoplasma and Trypanosome. 6,7 Host immune activation essential to eliminate intracellular pathogens is also negatively modulated by AKT 8 and constitutively active AKT was shown to increase the LPSinduced production of anti-inflammatory cytokine IL-10 (ref 9) and to down-regulate p65 and GSK-3β (ref 10). Two major proteins which contribute in diversifying AKT signaling are β-catenin and FOXO-1.…”

mentioning

confidence: 99%

Leishmania donovani inhibits macrophage apoptosis and pro-inflammatory response through AKT-mediated regulation of β-catenin and FOXO-1

et al. 2016

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In order to establish infection, intra-macrophage parasite Leishmania donovani needs to inhibit host defense parameters like inflammatory cytokine production and apoptosis. In the present study, we demonstrate that the parasite achieves both by exploiting a single host regulator AKT for modulating its downstream transcription factors, β-catenin and FOXO-1. L. donovaniinfected RAW264.7 and bone marrow-derived macrophages (BMDM) treated with AKT inhibitor or dominant negative AKT constructs showed decreased anti-inflammatory cytokine production and increased host cell apoptosis resulting in reduced parasite survival. Infection-induced activated AKT triggered phosphorylation-mediated deactivation of its downstream target, GSK-3β. Inactivated GSK-3β, in turn, could no longer sequester cytosolic β-catenin, an anti-apoptotic transcriptional regulator, as evidenced from its nuclear translocation during infection. Constitutively active GSK-3β-transfected L. donovani-infected cells mimicked the effects of AKT inhibition and siRNA-mediated silencing of β-catenin led to disruption of mitochondrial potential along with increased caspase-3 activity and IL-12 production leading to decreased parasite survival. In addition to activating antiapoptotic β-catenin, phospho-AKT inhibits activation of FOXO-1, a pro-apoptotic transcriptional regulator. Nuclear retention of FOXO-1, inhibited during infection, was reversed when infected cells were transfected with dominant negative AKT constructs. Overexpression of FOXO-1 in infected macrophages not only documented increased apoptosis but promoted enhanced TLR4 expression and NF-κB activity along with an increase in IL-1β and decrease in IL-10 secretion. In vivo administration of AKT inhibitor significantly decreased liver and spleen parasite burden and switched cytokine balance in favor of host. In contrast, GSK-3β inhibitor did not result in any significant change in infectivity parameters. Collectively our findings revealed that L. donovani triggered AKT activation to regulate GSK-3β/β-catenin/FOXO-1 axis, thus ensuring inhibition of both host cell apoptosis and immune response essential for its intra-macrophage survival.

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Staying alive: bacterial inhibition of apoptosis during infection

Cited by 132 publications

References 64 publications

Programmed cell death in the plant immune system

Programmed cell death in the plant immune system

Inhibition of Egr-1 by siRNA in prostate carcinoma cell lines is associated with decreased expression of AP-1 and NF-κB

Leishmania donovani inhibits macrophage apoptosis and pro-inflammatory response through AKT-mediated regulation of β-catenin and FOXO-1

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