<i>Yersinia enterocolitica</i>Induces Apoptosis and Inhibits Surface Molecule Expression and Cytokine Production in Murine Dendritic Cells

Erfurth, Stella; Gröbner, Sabine; Kramer, Uwe; Gunst, Dani S. J.; Soldanova, Irena; Schaller, Martin; Autenrieth, Ingo B.; Borgmann, Stefan

doi:10.1128/iai.72.12.7045-7054.2004

Cited by 68 publications

(100 citation statements)

References 32 publications

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“…Although best characterized in the effector cells of the innate immune system (macrophages, monocytes), it has become evident that Yersinia can also inject Yops into professional APC like DC [3], potentially altering both the adaptive cellular and humoral immune responses that DC play an essential role in initiating. While less is known about YopJ's effect on DC, YopP in Y. enterocolitica infection of fully differentiated DC has been implicated in mediating apoptosis (in murine DC), suppressing cytokine production, antigen presentation and immunostimulatory capacity [14,17,18]. In Y. pestis, YopJ appears to have less of a negative effect on the survival and immune function of differentiated murine DC, but rather has a marked effect on DC migration [19].…”

Section: Discussionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

“…(e.g. Y. enterocolitica) also can impair DC function and induce DC apoptosis (in mice) [14,17,18], and it has been recently shown that Y. pestis inhibits cellular migration in fully differentiated murine DC [19].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2007

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“…The pYV-encoded YopP protein is essential for the induction of apoptosis in macrophages 53 and simultaneously induces caspase-dependent apoptotic and caspase-independent necrotic cell death in dendritic cells. 54,55 In Hep2 cells, apoptosis has been shown to be invasin induced. 56 In contrast, Y. enterocolitica did not elevate the apoptotic rate in HT-29/B6 monolayers, but increased the level of necrotic cells.…”

Section: Necrosis and Apoptosis Induction By Y Enterocoliticamentioning

confidence: 99%

Yersinia enterocolitica induces epithelial barrier dysfunction through regional tight junction changes in colonic HT-29/B6 cell monolayers

Hering

Richter

Krug

et al. 2011

Laboratory Investigation

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Yersinia enterocolitica is a common cause of acute gastroenteritis. This study aimed to clarify the mechanisms leading to barrier dysfunction and diarrhea. Exposure of human colonic HT-29/B6 cells to Y. enterocolitica resulted in a decrease in transepithelial resistance from 404 ± 23 to 163 ± 21 O cm 2 (Po0.001) in parallel with an increase in mannitol (182 Da) and fluorescein (332 Da) permeability, whereas short circuit current did not change. This effect was time dependent, required the presence of living bacteria, could not be triggered by bacterial supernatants and was not due to Yersinia outer proteins. Concomitantly, Y. enterocolitica induced necrosis as indicated by an increase in lactate dehydrogenase-release, whereas epithelial apoptosis was not upregulated. Local changes in conductivity were detected by conductance scanning, indicating 'leaky regions' within the epithelium that were visualized by biotinylation and confocal microscopy. In these regions, claudin-3 and -4 and, especially claudin-8, were redistributed off the tight junction (TJ) into the cytoplasm. In addition, the expression of claudin-2, -3, -8, -10 and ZO-1 was diminished as quantified by immunoblotting. Moreover, we found claudin-8 to be regulated by the c-Jun N-terminal kinase, the inhibition of which attenuated the Y. enterocolitica-induced decrease in transepithelial resistance and restored claudin-8 protein level. In conclusion, barrier dysfunction in Y. enterocolitica infection is due to circumscribed epithelial TJ protein changes and necrotic cell loss, as a consequence of which leak flux diarrhea and antigen-uptake provoking extraintestinal arthritis may be triggered.

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“…Most research has been conducted on the pYV-encoded type III secretion system, responsible for injection of Yop effector proteins into host cells (Cornelis & Wolf-Watz, 1997). The Yop proteins are responsible for a large number of virulence traits, including the avoidance of macrophage ingestion (Grosdent et al, 2002), immunomodulation (Boland & Cornelis, 1998;Carlos et al, 2004;Denecker et al, 2002;Erfurth et al, 2004) and cytotoxicity (Andor et al, 2001;Zumbihl et al, 1999). The majority of the remaining research on pathogenesis of Y. enterocolitica has focused on invasin, and the adhesins Ail and YadA.…”

Section: Introductionmentioning

confidence: 99%

An aflagellate mutant Yersinia enterocolitica biotype 1A strain displays altered invasion of epithelial cells, persistence in macrophages, and cytokine secretion profiles in vitro

et al. 2007

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Yersinia enterocoliticaInduces Apoptosis and Inhibits Surface Molecule Expression and Cytokine Production in Murine Dendritic Cells

Cited by 68 publications

References 32 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

Yersinia enterocolitica induces epithelial barrier dysfunction through regional tight junction changes in colonic HT-29/B6 cell monolayers

An aflagellate mutant Yersinia enterocolitica biotype 1A strain displays altered invasion of epithelial cells, persistence in macrophages, and cytokine secretion profiles in vitro

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