<i>Salmonella</i>‐induced SipB‐independent cell death requires Toll‐like receptor‐4 signalling via the adapter proteins Tram and Trif

Cook, Paul; Tötemeyer, Sabine; Stevenson, Catherine; Fitzgerald, Katherine A.; Yamamoto, Masahiro; Akira, Shizuo; Maskell, Duncan J.; Bryant, Clare E.

doi:10.1111/j.1365-2567.2007.02631.x

Cited by 18 publications

(16 citation statements)

References 50 publications

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“…We also showed that SPI1, but not SPI2 was related with c-Myc protein level and cell death. This conclusion is consistent with the report that apoptosis in macrophages in response to S. typhimurium infection is rapid, specific, and depend on the type III secretion system encoded within SPI1 (Cook et al, 2007). Here, we reported that Salmonella infection increased c-Myc protein level in host cells during bacterial endocytosis and sequentially induced host cell death.…”

Section: Salmonella Typhimurium C-myc Infection Ornithine Decarboxsupporting

confidence: 94%

Expression of c-Myc is related to host cell death following Salmonella typhimurium infection in macrophage

et al. 2009

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It has been known that ornithine decarboxylase (ODC) induced by the binding of c-Myc to odc gene is closely linked to cell death. Here, we investigated the relationship between their expressions and cell death in macrophage cells following treatment with Salmonella typhimurium or lipopolysaccharide (LPS). ODC expression was increased by bacteria or LPS and repressed by inhibitors against mitogen-activated protein kinases (MAPKs) in Toll-like receptor 4 (TLR4) signaling pathway. In contrast, c-Myc protein level was increased after treatment with bacteria, but not by treatment with LPS or heat-killed bacteria although both bacteria and LPS increased the levels of c-myc mRNA to a similar extent. c-Myc protein level is dependent upon bacterial invasion because treatment with cytochalasin D (CCD), inhibitors of endocytosis, decreased c-Myc protein level. The cell death induced by bacteria was significantly decreased after treatment of CCD or c-Myc inhibitor, indicating that cell death by S. typhimurium infection is related to c-Myc, but not ODC. Consistent with this conclusion, treatment with bacteria mutated to host invasion did not increase c-Myc protein level and cell death rate. Taken together, it is suggested that induction of c-Myc by live bacterial infection is directly related to host cell death.

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Section: Salmonella Typhimurium C-myc Infection Ornithine Decarboxsupporting

confidence: 94%

Expression of c-Myc is related to host cell death following Salmonella typhimurium infection in macrophage

et al. 2009

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“…Wildtype BMMs exhibited greater cell death relative to each of the other genotypes (Figure 3D, E). Because only wildtype BMMs express functional TLR4, the increased death of these cells seems likely due to a previously described TLR4-dependent cell death that occurs in S. typhimurium infected cells (Cook et al, 2007; Hsu et al, 2004; Park et al, 2002). Thus, the apparent lack of replication as measured by CFU in wildtype BMMs is the result of macrophage death followed by gentamicin-mediated killing of the bacteria.…”

Section: Resultsmentioning

confidence: 90%

TLR Signaling Is Required for Salmonella typhimurium Virulence

Arpaia

Godec

Lau

et al. 2011

Cell

222

213

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Summary Toll-like receptors (TLRs) contribute to host resistance to microbial pathogens and drive the evolution of virulence mechanisms. We have examined the relationship between host resistance and pathogen virulence using mice with a functional allele of the Nramp-1 gene and lacking combinations of TLRs. Mice deficient in both TLR2 and TLR4 were highly susceptible to the intracellular bacterial pathogen Salmonella typhimurium, consistent with reduced innate immune function. However, mice lacking additional TLRs involved in S. typhimurium recognition were less susceptible to infection. In these TLR-deficient cells, bacteria failed to upregulate Salmonella pathogenicity island 2 (SPI-2) genes and did not form a replicative compartment. We demonstrate that TLR signaling enhances the rate of acidification of the Salmonella containing phagosome, and inhibition of this acidification prevents SPI-2 induction. Our results indicate that S. typhimurium requires cues from the innate immune system to regulate virulence genes necessary for intracellular survival, growth, and systemic infection.

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“…Interestingly, while flagellin is able to activate caspase-1 in BMDM in vitro (12,38), we found flagellin to be dispensable for caspase-1-dependent Ifng transcription in the cecal mucosae of mice. An alternative mechanism for activating caspase-1 involves TLR4 and the ATP-sensitive purinergic P2X 7 receptor; however, serotype Typhimurium does not activate the inflammasome through this pathway in vitro (10,13). Additional work is needed to identify the bacterial pathogen-associated molecular pattern and its cognate host NLR responsible for caspase-1- dependent IFN-␥ production in the intestine of streptomycinpretreated mice early after serotype Typhimurium infection.…”

Section: Discussionmentioning

confidence: 99%

Contribution of Flagellin Pattern Recognition to Intestinal Inflammation duringSalmonella entericaSerotype Typhimurium Infection

et al. 2009

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Salmonella enterica serotype Typhimurium causes acute inflammatory diarrhea in humans. Flagella contribute to intestinal inflammation, but the mechanism remains unclear since most mutations abrogating pattern recognition of flagellin also prevent motility and reduce bacterial invasion. To determine the contribution of flagellin pattern recognition to the generation of innate immune responses, we compared in two animal models a nonmotile, but flagellin-expressing and -secreting serotype Typhimurium strain (flgK mutant) to a nonmotile, non-flagellin-expressing strain (flgK fliC fljB mutant). In vitro, caspase-1 can be activated by cytosolic delivery of flagellin, resulting in release of the interferon gamma inducing factor interleukin-18 (IL-18). Experiments with streptomycin-pretreated caspase-1-deficient mice suggested that induction of gamma interferon expression in the murine cecum early (12 h) after serotype Typhimurium infection was caspase-1 dependent but independent of flagellin pattern recognition. In addition, mRNA levels of the CXC chemokines macrophage inflammatory protein 2 and keratinocyte-derived chemokine were markedly increased early after serotype Typhimurium infection of streptomycin-pretreated wild-type mice regardless of flagellin expression. In contrast, in bovine ligated ileal loops, flagellin pattern recognition contributed to increased mRNA levels of macrophage inflammatory protein 3␣ and more fluid accumulation at 2 h after infection. Collectively, our data suggest that pattern recognition of flagellin contributes to early innate host responses in the bovine ileal mucosa but not in the murine cecal mucosa.Salmonella enterica serotype Typhimurium is a major cause of gastroenteritis in humans, which is characterized by acute intestinal inflammation and diarrhea (11,36). One of the serotype Typhimurium virulence factors contributing to intestinal inflammation are flagella. Nonflagellated serotype Typhimurium mutants have been shown to cause less inflammation than their isogenic parents do after infection of bovine ligated ileal loops (59), streptomycin-pretreated mice (65, 74), and chickens (24).Several possible mechanisms by which flagella may contribute to eliciting proinflammatory responses have been proposed. Flagella are surface appendages of serotype Typhimurium that are required for motility and chemotaxis. Motility contributes to serotype Typhimurium invasion of intestinal epithelial cell lines by increasing bacterial contact with host cells (26,27). The invasion-associated type III secretion system (T3SS-1) is important for inducing intestinal inflammation in animal models (1,20,70,81). Nonmotile serotype Typhimurium mutants may thus cause reduced intestinal inflammation in vivo because the efficiency of T3SS-1-mediated invasion is reduced.In addition to its role in motility and invasion, the proteinaceous monomer of the flagellar filament, flagellin, has been shown to be a potent activator of the innate immune response in tissue culture models. Flagellin is an agonist of Toll-like ...

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Salmonella‐induced SipB‐independent cell death requires Toll‐like receptor‐4 signalling via the adapter proteins Tram and Trif

Cited by 18 publications

References 50 publications

Expression of c-Myc is related to host cell death following Salmonella typhimurium infection in macrophage

Expression of c-Myc is related to host cell death following Salmonella typhimurium infection in macrophage

TLR Signaling Is Required for Salmonella typhimurium Virulence

Contribution of Flagellin Pattern Recognition to Intestinal Inflammation duringSalmonella entericaSerotype Typhimurium Infection

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