The<i>Salmonella</i>invasin SipB induces macrophage apoptosis by binding to caspase-1

Hersh, David; Monack, Denise M.; Smith, Mark R.; Ghori, Nafisa; Falkow, Stanley; Zychlinsky, Arturo

doi:10.1073/pnas.96.5.2396

Cited by 694 publications

(602 citation statements)

References 37 publications

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“…14 Modulation of the gene expression has been found to be essential for the pathogenicity of Salmonella infection. 15 Serum and glucocorticoid-inducible kinase (SGK) is a serine/threonine protein kinase shown to be important in activating Upregulated 87 a 69 70 119 91 24 Downregulated 14 17 7 3 3 7 Total 101 86 77 122 94 31 a Numbers indicate the number of genes in peripheral blood of patients with ulceroglandular tularemia with a ratio at least twofold up-or downregulated compared to a control pool from eight healthy volunteers and with a B value above zero. Ninety-five genes were regulated at more than one time point but not in the convalescent samples.…”

Section: Resultsmentioning

confidence: 99%

Transcriptional profiling of the peripheral blood response during tularemia

et al. 2006

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Tularemia is a febrile disease caused by the highly contagious bacterium Francisella tularensis. We undertook an analysis of the transcriptional response in peripheral blood during the course of ulceroglandular tularemia by use of Affymetrix microarrays comprising 14 500 genes. Samples were obtained from seven individuals at five occasions during 2 weeks after the first hospital visit and convalescent samples 3 months later. In total, 265 genes were differentially expressed, 95 of which at more than one time point. The differential expression was verified with real-time quantitative polymerase chain reaction for 36 genes (R 2 ¼ 0.590). The most prominent changes were noted in samples drawn on days 2-3 and a considerable proportion of the upregulated genes appeared to represent an interferon-g-induced response and also a proapoptotic response. Genes involved in the generation of innate and acquired immune responses were found to be downregulated, presumably a pathogen-induced event. A logistic regression analysis revealed that seven genes were good predictors of the early phase of tularemia. This is the first description of the transcriptional host response to ulceroglandular tularemia and the study has identified gene subsets relevant to the pathogenesis of the disease and subsets that may serve as early diagnostic biomarkers.

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Section: Resultsmentioning

confidence: 99%

Transcriptional profiling of the peripheral blood response during tularemia

et al. 2006

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“…Modulation of this mechanism in the cells encountered in the various tissues of the RES may provide an excellent strategy to evade the immune system. In particular, macrophage apoptosis induced by salmonella signals, appears to require SipB translocation into the cytoplasm via the salmonella type III secretion system [223] and prior activation of the macrophage [217]. Therefore, salmonella hides itself inside the monocytemacrophage but it may ' decide ' to kill this host cell when it become activated, inducing a pathway, apoptosis, that limits inflammation and allows the bacteria to remain intracellular.…”

Section: Extraintestinal Infection : Interaction With the Reticulo-enmentioning

confidence: 99%

Host adapted serotypes of Salmonella enterica

et al. 2000

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Salmonella constitutes a genus of zoonotic bacteria of worldwide economic and health importance. The current view of salmonella taxonomy assigns the members of this genus to two species: S. enterica and S. bongori. S. enterica itself is divided into six subspecies, enterica, salamae, arizonae, diarizonae, indica, and houtenae, also known as subspecies I, II, IIIa, IIIb, IV, and VI, respectively [1]. Members of Salmonella enterica subspecies enterica are mainly associated with warm-blooded vertebrates and are usually transmitted by ingestion of food or water contaminated by infected faeces. The pathogenicity of most of the distinct serotypes remains undefined, and even within the most common serotypes, many questions remain to be answered regarding the interactions between the organism and the infected host.Salmonellosis manifests itself in three major forms: enteritis, septicaemia, and abortion, each of which may be present singly or in combination, depending on both the serotype and the host involved. Although currently over 2300 serovars of Salmonella are recognized, only about 50 serotypes are isolated in any significant numbers as human or animal pathogens [2, 3] and they all belong to subspecies enterica. Of these, most cause acute gastroenteritis characterized by a short incubation period and a severe systemic disease in man or animals, characterized by septicaemia, fever and/or abortion, and such serotypes are often associated with one or few host species [4–6].It is the intention of this review to present a summary of current knowledge of these host-adapted serotypes of S. enterica. The taxonomic relationships between the serotypes will be discussed together with a comparison of the pathology and pathogenesis of the disease that they cause in their natural host(s). Since much of our knowledge on salmonellosis is based on the results of work on Typhimurium, this serotype will often be used as the baseline in discussion. It is hoped that an appreciation of the differences that exist in the way these serotypes interact with the host will lead to a greater understanding of the complex host–parasite relationship that characterizes salmonella infections.

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“…SopB is also involved in host cell survival through activation of the Akt signaling pathway [16,18,19]. Additional functions have recently been described for SPI-1, including activation of the host innate immune system and induction of cell death [20,21]. SipA induces the recruitment of polymorphonuclear cells across the epithelial barrier [21], while SipB is involved in the induction of pyroptotic cell death in macrophages [20].…”

Section: Introductionmentioning

confidence: 99%

“…Additional functions have recently been described for SPI-1, including activation of the host innate immune system and induction of cell death [20,21]. SipA induces the recruitment of polymorphonuclear cells across the epithelial barrier [21], while SipB is involved in the induction of pyroptotic cell death in macrophages [20]. Moreover, the T3SS encoded by SPI-1 (T3SS-1) is required to activate the Nod-like receptor (NLR) family CARD domain-containing protein 4 (NLRC4) inflammasome complex in macrophages [22].…”

Section: Introductionmentioning

confidence: 99%

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SopB activates the Akt-YAP pathway to promote Salmonella survival within B cells

et al. 2018

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B cells are a target of Salmonella infection, allowing bacteria survival without inducing pyroptosis. This event is due to downregulation of Nlrc4 expression and lack of inflammasome complex activation, which impairs the secretion of IL-1β. YAP phosphorylation is required for downregulation of Nlrc4 in B cells during Salmonella infection; however, the microorganism’s mechanisms underlying the inhibition of the NLRC4 inflammasome in B cells are not fully understood. Our findings demonstrate that the Salmonella effector SopB triggers a signaling cascade involving PI3K, PDK1 and mTORC2 that activates Akt with consequent phosphorylation of YAP. When we deleted sopB in Salmonella, infected B cells that lack Rictor, or inhibited the signaling cascade using a pharmacological approach, we were able to restore the function of the NLRC4 inflammasome in B cells and the ability to control the infection. Furthermore, B cells from infected mice exhibited activation of Akt and YAP phosphorylation, suggesting that Salmonella also triggers this pathway in vivo. In summary, our data demonstrate that the Salmonella effector inositide phosphate phosphatase SopB triggers the PI3K-Akt-YAP pathway to inhibit the NLRC4 inflammasome in B cells. This study provides further evidence that Salmonella triggers cellular mechanisms in B lymphocytes to manipulate the host environment by turning it into a survival niche to establish a successful infection.

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TheSalmonellainvasin SipB induces macrophage apoptosis by binding to caspase-1

Cited by 694 publications

References 37 publications

Transcriptional profiling of the peripheral blood response during tularemia

Transcriptional profiling of the peripheral blood response during tularemia

Host adapted serotypes of Salmonella enterica

SopB activates the Akt-YAP pathway to promote Salmonella survival within B cells

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