Proinflammatory signalling stimulated by the type III translocation factor YopB is counteracted by multiple effectors in epithelial cells infected with <i> Yersinia pseudotuberculosis</i>

Viboud, Gloria I.; So, Stephane Shu Kin; Ryndak, Michelle B.; Bliska, James B.

doi:10.1046/j.1365-2958.2003.03350.x

Cited by 72 publications

(82 citation statements)

References 53 publications

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“…It is, therefore, possible that the differences seen above are due to YopB and not YopJ, as YopB can also affect eukaryotic signal transduction [36]. To assess this, we examined the effects of Y. pestis KIM5-3001.48 (YopB + YopJ -), a injection competent poly-yop deletion mutant either carrying (YopB + YopJ + ) or not carrying (YopB + YopJ -) the pYopJ-GSK plasmid.…”

Section: Effect Of Injection Competent Vs Incompetent Strains Of Y mentioning

confidence: 99%

Modulation of dendritic cell differentiation and function by YopJ of Yersinia pestis

et al. 2007

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Yersinia pestis evades immune responses in part by injecting into host immune cells several effector proteins called Yersinia outer proteins (Yops) that impair cellular function. This has been best characterized in the innate effector cells, but much less so for cells involved in adaptive immune responses. Dendritic cells (DC) sit at the crossroads between innate and adaptive immunity, and can function to initiate or inhibit adaptive immune responses. Although Y. pestis can target and inactivate DC, the mechanism responsible for this remains unclear. We have found that injection of Y. pestis YopJ into DC progenitors disrupts key signal transduction pathways and interferes with DC differentiation and subsequent function. YopJ injection prevents upregulation of the NF-jB transcription factor Rel B and inhibits MAPK/ERK activationboth having key roles in DC differentiation. Furthermore, YopJ injection prevents costimulatory ligand up-regulation, LPS-induced cytokine expression, and yields differentiated DC with diminished capability to induce T cell proliferation and IFN-c induction. By modulating DC function through YopJ-mediated disruption of signaling pathways during progenitor to DC differentiation, Yersinia may interfere with the adaptive responses necessary to clear the infection as well as establish a tolerant immune environment that leads to chronic infection/carrier state in the surviving host.

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Section: Effect Of Injection Competent Vs Incompetent Strains Of Y mentioning

confidence: 99%

Modulation of dendritic cell differentiation and function by YopJ of Yersinia pestis

et al. 2007

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“…to activate NF-B, which subsequently gives rise to a proinflammatory host cell response, including production of, e.g., IL-8 (17,39,(45)(46)(47). NF-B is a key transcription factor involved in innate immune responses to pathogens (9).…”

Section: Resultsmentioning

confidence: 99%

Trimer Stability of YadA Is Critical for Virulence of Yersinia enterocolitica

et al. 2010

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Yersinia adhesin A (YadA) is a trimeric autotransporter adhesin with multiple functions in host-pathogen interactions. The aim of this study was to dissect the virulence functions promoted by YadA in vitro and in vivo. To accomplish this, we generated Yersinia enterocolitica O:8 mutants expressing point mutations in YadA G389, a highly conserved residue in the membrane anchor of YadA, and analyzed their impact on YadA expression and virulence functions. We found that point mutations of YadA G389 led to impaired transport, stability, and surface display of YadA. YadA G389A and G389S mutants showed comparable YadA surface expression, autoagglutination, and adhesion to those of wild-type YadA but displayed reduced trimer stability and complement resistance in vitro and were 10-to 1,000-fold attenuated in experimental Y. enterocolitica infection in mice. The G389T, G389N, and G389H mutants lost trimer stability, exhibited strongly reduced surface display, autoagglutination, adhesion properties, and complement resistance, and were avirulent (>10,000-fold attenuation) in mice. Our data demonstrate that G389 is a critical residue of YadA, required for optimal trimer stability, transport, surface display, and serum resistance. We also show that stable trimeric YadA protein is essential for virulence of Y. enterocolitica.

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“…The repressive mechanisms responsible depend on bacterial injection of host cells with type III secretion effectors. For example, the Y. pestis secreted effector YopJ is a potent inhibitor of the NF-kB and MAPK signalling pathways (Sweet et al, 2007), and YopE has been shown to strongly inhibit activation of JNK, ERK and NF-kB with a coincident suppression of interleukin (IL)-8 production (Viboud & Bliska, 2005;Viboud et al, 2003). The Yersinia V-antigen has been reported to induce IL-10, which represses innate immunity (Brubaker, 2003;Overheim et al, 2005;Philipovskiy et al, 2005) but this activity has been challenged in more recent reports (Pouliot et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Induction of innate immunity by lipid A mimetics increases survival from pneumonic plague

et al. 2008

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This study analysed the effect of priming the innate immune system using synthetic lipid A mimetics in a Yersinia pestis murine pulmonary infection model. Two aminoalkyl glucosaminide 4-phosphate (AGP) Toll-like receptor 4 (TLR4) ligands, delivered intranasally, extended time to death or protected against a lethal Y. pestis CO92 challenge. The level of protection was dependent upon the challenge dose of Y. pestis and the timing of AGP therapy. Protection correlated with cytokine induction and a decreased bacterial burden in lung tissue. AGP protection was TLR4-dependent and was not evidenced in transgenic TLR4-deficient mice. AGP therapy augmented with subtherapeutic doses of gentamicin produced dramatically enhanced survival. Combined, these results indicated that AGPs may be useful in protection of immunologically naive individuals against plague and potentially other infectious agents, and that AGP therapy may be used synergistically with other therapies.

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Proinflammatory signalling stimulated by the type III translocation factor YopB is counteracted by multiple effectors in epithelial cells infected with Yersinia pseudotuberculosis

Abstract: Summary

Cited by 72 publications

References 53 publications

Modulation of dendritic cell differentiation and function by YopJ of Yersinia pestis

Modulation of dendritic cell differentiation and function by YopJ of Yersinia pestis

Trimer Stability of YadA Is Critical for Virulence of Yersinia enterocolitica

Induction of innate immunity by lipid A mimetics increases survival from pneumonic plague

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