Cytotoxicity and interleukin-1β processing following Shigella flexneri infection of human monocyte-derived dendritic cells

Edgeworth, Jonathan D; Spencer, Jo; Phalipon, Armelle; Griffin, George E.; Sansonetti, Philippe J.

doi:10.1002/1521-4141(200205)32:5<1464::aid-immu1464>3.0.co;2-g

Cited by 70 publications

(45 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This mechanism likely involves rapid shedding of evaginated microvesicles (24) and/or exocytosis of exosomes packaged within specialized secretory lysosomes (25) before the delayed onset of cytolysis. The mechanism by which glycine confers protection against ATP-induced cytotoxicity is unknown but it is significant to note that glycine produces a similar blockade of the macrophage death induced by Salmonella or Shigella infection (55,57).…”

Section: (43) Manipulation Of Extracellular CLsupporting

confidence: 85%

“…potentiated cytolysis in parallel with its effects on IL-1␤ release is consistent with a role for caspase-1 in ATP-induced cytolysis as also proposed by Le Feuvre et al (28). Interestingly, infection of macrophages with Salmonella or Shigella also induces a coordinated activation of caspase-1 followed by rapid cell death (55)(56)(57). However, the ability of glycine to greatly reduce ATP-elicited cytolysis while only partially diminishing IL-1␤ release indicates that the regulated secretion of mIL-1␤ can be dissociated from rapid macrophage death.…”

Section: (43) Manipulation Of Extracellular CLmentioning

confidence: 99%

See 1 more Smart Citation

Inhibitory Effects of Chloride on the Activation of Caspase-1, IL-1β Secretion, and Cytolysis by the P2X7 Receptor

Verhoef¹,

Kertesy²,

Lundberg³

et al. 2005

The Journal of Immunology

107

View full text Add to dashboard Cite

The P2X7 receptor (P2X7R) is an ATP-gated cation channel that activates caspase-1 leading to the maturation and secretion of IL-1β. Because previous studies indicated that extracellular Cl− exerts a negative allosteric effect on ATP-gating of P2X7R channels, we tested whether Cl− attenuates the P2X7R→caspase-1→IL-1β signaling cascade in murine and human macrophages. In Bac1 murine macrophages, substitution of extracellular Cl− with gluconate produced a 10-fold increase in the rate and extent of ATP-induced IL-1β processing and secretion, while reducing the EC50 for ATP by 5-fold. Replacement of Cl− with gluconate also increased the potency of ATP as an inducer of mature IL-1β secretion in primary mouse bone marrow-derived macrophages and in THP-1 human monocytes/macrophages. Our observations were consistent with actions of Cl− at three levels: 1) a negative allosteric effect of Cl−, which limits the ability of ATP to gate the P2X7R-mediated cation fluxes that trigger caspase-1 activation; 2) an intracellular accumulation of Cl− via nonselective pores induced by P2X7R with consequential repression of caspase-1-mediated processing of IL-1β; and 3) a facilitative effect of Cl− substitution on the cytolytic release of unprocessed pro-IL-1β that occurs with sustained activation of P2X7R. This cytolysis was repressed by the cytoprotectant glycine, permitting dissociation of P2X7R-regulated secretion of mature IL-1β from the lytic release of pro-IL-1β. These results suggest that under physiological conditions P2X7R are maintained in a conformationally restrained state that limits channel gating and coupling of the receptor to signaling pathways that regulate caspase-1.

show abstract

Section: (43) Manipulation Of Extracellular CLsupporting

confidence: 85%

Section: (43) Manipulation Of Extracellular CLmentioning

confidence: 99%

Inhibitory Effects of Chloride on the Activation of Caspase-1, IL-1β Secretion, and Cytolysis by the P2X7 Receptor

Verhoef¹,

Kertesy²,

Lundberg³

et al. 2005

The Journal of Immunology

107

View full text Add to dashboard Cite

show abstract

“…The intestinal In striking contrast, many studies report that Salmonella is internalized by and survives within both human and murine DCs (6,9,18,29,45), although Salmonella has been reported to rapidly kill infected DCs and macrophages (21,25,48). Shigella infection of human DCs results in rapid IpaB-dependent DC death (8), which probably dampens the adaptive immune response to this enteric pathogen. Similar to our findings with Campylobacter, Y. enterocolitica enters DCs and does not induce necrosis or apoptosis (40).…”

Section: Discussionmentioning

confidence: 99%

“…Helicobacter pylori also induces maturation and cytokine release from human DCs (24). Shigella flexneri infection of DCs leads to up-regulation of interleukin-1␤ (IL-1␤) and IL-18 and rapid DC death (8). In contrast, Yersinia enterocolitica is able to invade DCs and does not induce necrosis or apoptosis but impairs DC function (40).…”

mentioning

confidence: 99%

Campylobacter jejuniInduces Maturation and Cytokine Production in Human Dendritic Cells

Bray

Osorio

et al. 2006

Infect Immun

View full text Add to dashboard Cite

Campylobacter jejuni is a leading bacterial cause of human diarrheal disease in both developed and developing nations. Colonic mucosal invasion and the resulting host inflammatory responses are thought to be the key contributing factors to the dysenteric form of this disease. Dendritic cells (DCs) play an important role in both the innate and adaptive immune responses to microbial infection. In this study, the interaction between human monocyte-derived dendritic cells and C. jejuni was studied. We found that C. jejuni was readily internalized by DCs over a 2-h period. However, after a prolonged infection period (24 or 48 h) with C. jejuni, only a few viable bacteria remained intracellularly. Minimal cytotoxicity of C. jejuni to dendritic cells was observed. C. jejuni induced the maturation of dendritic cells over 24 h, as indicated by up-regulation of cell surface marker proteins CD40, CD80, and CD86. In addition, Campylobacter-infected DCs triggered activation of NF-B and significantly stimulated production of interleukin-1␤ (IL-1␤), IL-6, IL-8, IL-10, IL-12, gamma interferon, and tumor necrosis factor alpha (TNF-␣) compared to uninfected DCs. Active bacterial invasion of DCs was not necessary for the induction of these cytokines, as heat-killed C. jejuni stimulated similar levels of cytokine production as live bacteria. Purified lipooligosaccharide of C. jejuni appears to be the major stimulant for the increased production of cytokines by DCs. Taken together, these data indicate that during infection, Campylobacter triggers an innate inflammatory response through increased production of IL-1␤, IL-6, IL-8, and TNF-␣ and initiates a Th1-polarized adaptive immune response as predicted from the high level of production of IL-12.

show abstract

“…Previous studies have shown that intracytosolic Shigella that have escaped from phagosomes induce death of the infected macrophages and dendritic cells (7,42), and that components common to Gram-negative bacteria induce necrotic cell death and caspase-1 activation (7). Mouse J774 macrophages were infected with wildtype Shigella, ⌬virG (conventional attenuated vaccine strain), ⌬ipaB, and ⌬ipaB/inv to determine whether ⌬ipaB/inv was capable of inducing cell death.…”

Section: Generation and Characterization Of An Invasin-expressing Shimentioning

confidence: 99%

High Vaccine Efficacy against Shigellosis of Recombinant Noninvasive Shigella Mutant That Expresses Yersinia Invasin

Suzuki

Yoshikawa

Ashida

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

Live attenuated Shigella vaccines elicit protective immune responses, but involve a potential risk of inducing a strong inflammatory reaction. The bacterial invasiveness that is crucial for Ag delivery causes inflammatory destruction of infected epithelial cells and proinflammatory cell death of infected macrophages. In this study, the noninvasive Shigella mutant ΔipaB was equipped with Yersinia invasin protein, which has been shown to mediate bacterial invasion and targeting to M cells located in follicle-associated epithelium. Invasin-expressing ΔipaB (ΔipaB/inv) was internalized into epithelial cells and retained in the intraphagosomal space. ΔipaB/inv did not induce necrotic cell death of infected macrophages nor cause symptomatic damage after intranasal vaccination of mice. ΔipaB/inv was safer and more effective than the conventional live vaccine, ΔvirG. Infection by ΔipaB/inv caused polymorphonuclear neutrophil infiltration in the lung, but did not induce production of large amounts of proinflammatory cytokines. We concluded that the low experimental morbidity and high vaccine efficacy of ΔipaB/inv are primarily based on high protective immune responses, which may be enhanced by the polymorphonuclear neutrophil infiltration unaccompanied by tissue injury.

show abstract

Cytotoxicity and interleukin-1β processing following Shigella flexneri infection of human monocyte-derived dendritic cells

Cited by 70 publications

References 35 publications

Inhibitory Effects of Chloride on the Activation of Caspase-1, IL-1β Secretion, and Cytolysis by the P2X7 Receptor

Inhibitory Effects of Chloride on the Activation of Caspase-1, IL-1β Secretion, and Cytolysis by the P2X7 Receptor

Campylobacter jejuniInduces Maturation and Cytokine Production in Human Dendritic Cells

High Vaccine Efficacy against Shigellosis of Recombinant Noninvasive Shigella Mutant That Expresses Yersinia Invasin

Contact Info

Product

Resources

About