The Experts below are selected from a list of 261 Experts worldwide ranked by ideXlab platform
Mark A. Jepson - One of the best experts on this subject based on the ideXlab platform.
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M-Cell Surface β1 Integrin Expression and Invasin-Mediated Targeting of Yersinia Pseudotuberculosis to Mouse Peyer’s Patch M Cells
Infection and immunity, 1998Co-Authors: M. Ann Clark, Barry H. Hirst, Mark A. JepsonAbstract:Quantitative analysis of Yersinia Pseudotuberculosis Infection of murine gut loops revealed that significantly more wild-type bacteria associated with Peyer’s patch M cells than with dome enterocytes or goblet cells. An invasin-deficient mutant was significantly attenuated for M-cell invasion, while β1 integrin expression was demonstrated in the apical membranes of M cells but not enterocytes. M-cell targeting by Yersinia Pseudotuberculosis in vivo may, therefore, be mediated primarily by the interaction of invasin with cell surface β1 integrins.
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m cell surface β1 integrin expression and invasin mediated targeting of Yersinia Pseudotuberculosis to mouse peyer s patch m cells
Infection and Immunity, 1998Co-Authors: Ann M Clark, Barry H. Hirst, Mark A. JepsonAbstract:Quantitative analysis of Yersinia Pseudotuberculosis Infection of murine gut loops revealed that significantly more wild-type bacteria associated with Peyer’s patch M cells than with dome enterocytes or goblet cells. An invasin-deficient mutant was significantly attenuated for M-cell invasion, while β1 integrin expression was demonstrated in the apical membranes of M cells but not enterocytes. M-cell targeting by Yersinia Pseudotuberculosis in vivo may, therefore, be mediated primarily by the interaction of invasin with cell surface β1 integrins.
Molly A. Bergman - One of the best experts on this subject based on the ideXlab platform.
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YopE specific CD8+ T cells provide protection against systemic and mucosal Yersinia Pseudotuberculosis Infection.
PloS one, 2017Co-Authors: Norberto González-juarbe, Haiqian Shen, Molly A. Bergman, Carlos J. Orihuela, Peter H. DubeAbstract:Prior studies indicated that CD8+ T cells responding to a surrogate single antigen expressed by Y. Pseudotuberculosis, ovalbumin, were insufficient to protect against yersiniosis. Herein we tested the hypothesis that CD8+ T cells reactive to the natural Yersinia antigen YopE would be more effective at providing mucosal protection. We first confirmed that immunization with the attenuated ksgA- strain of Y. Pseudotuberculosis generated YopE-specific CD8+ T cells. These T cells were protective against challenge with virulent Listeria monocytogenes expressing secreted YopE. Mice immunized with an attenuated L. monocytogenes YopE+ strain generated large numbers of functional YopE-specific CD8+ T cells, and initially controlled a systemic challenge with virulent Y. Pseudotuberculosis, yet eventually succumbed to yersiniosis. Mice vaccinated with a YopE peptide and cholera toxin vaccine generated robust T cell responses, providing protection to 60% of the mice challenged mucosally but failed to show complete protection against systemic Infection with virulent Y. Pseudotuberculosis. These studies demonstrate that vaccination with recombinant YopE vaccines can generate YopE-specific CD8+ T cells, that can provide significant mucosal protection but these cells are insufficient to provide sterilizing immunity against systemic Y. Pseudotuberculosis Infection. Our studies have implications for Yersinia vaccine development studies.
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YopE specific CD8+ T cells provide protection against systemic and mucosal Yersinia Pseudotuberculosis Infection - Table 1
2017Co-Authors: Norberto González-juarbe, Haiqian Shen, Molly A. Bergman, Carlos J. Orihuela, Peter H. DubeAbstract:YopE specific CD8+ T cells provide protection against systemic and mucosal Yersinia Pseudotuberculosis Infection - Table
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cd8 t cells restrict Yersinia Pseudotuberculosis Infection bypass of anti phagocytosis by targeting antigen presenting cells
PLOS Pathogens, 2009Co-Authors: Molly A. Bergman, Wendy P Loomis, Joan Mecsas, Michael N Starnbach, Ralph R IsbergAbstract:All Yersinia species target and bind to phagocytic cells, but uptake and destruction of bacteria are prevented by injection of anti-phagocytic Yop proteins into the host cell. Here we provide evidence that CD8+ T cells, which canonically eliminate intracellular pathogens, are important for restricting Yersinia, even though bacteria are primarily found in an extracellular locale during the course of disease. In a model of Infection with attenuated Y. Pseudotuberculosis, mice deficient for CD8+ T cells were more susceptible to Infection than immunocompetent mice. Although exposure to attenuated Y. Pseudotuberculosis generated TH1-type antibody responses and conferred protection against challenge with fully virulent bacteria, depletion of CD8+ T cells during challenge severely compromised protective immunity. Strikingly, mice lacking the T cell effector molecule perforin also succumbed to Y. Pseudotuberculosis Infection. Given that the function of perforin is to kill antigen-presenting cells, we reasoned that cell death marks bacteria-associated host cells for internalization by neighboring phagocytes, thus allowing ingestion and clearance of the attached bacteria. Supportive of this model, cytolytic T cell killing of Y. Pseudotuberculosis–associated host cells results in engulfment by neighboring phagocytes of both bacteria and target cells, bypassing anti-phagocytosis. Our findings are consistent with a novel function for cell-mediated immune responses protecting against extracellular pathogens like Yersinia: perforin and CD8+ T cells are critical for hosts to overcome the anti-phagocytic action of Yops.
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CD8(+) T cells restrict Yersinia Pseudotuberculosis Infection: bypass of anti-phagocytosis by targeting antigen-presenting cells.
PLoS pathogens, 2009Co-Authors: Molly A. Bergman, Wendy P Loomis, Joan Mecsas, Michael N Starnbach, Ralph R IsbergAbstract:All Yersinia species target and bind to phagocytic cells, but uptake and destruction of bacteria are prevented by injection of anti-phagocytic Yop proteins into the host cell. Here we provide evidence that CD8+ T cells, which canonically eliminate intracellular pathogens, are important for restricting Yersinia, even though bacteria are primarily found in an extracellular locale during the course of disease. In a model of Infection with attenuated Y. Pseudotuberculosis, mice deficient for CD8+ T cells were more susceptible to Infection than immunocompetent mice. Although exposure to attenuated Y. Pseudotuberculosis generated TH1-type antibody responses and conferred protection against challenge with fully virulent bacteria, depletion of CD8+ T cells during challenge severely compromised protective immunity. Strikingly, mice lacking the T cell effector molecule perforin also succumbed to Y. Pseudotuberculosis Infection. Given that the function of perforin is to kill antigen-presenting cells, we reasoned that cell death marks bacteria-associated host cells for internalization by neighboring phagocytes, thus allowing ingestion and clearance of the attached bacteria. Supportive of this model, cytolytic T cell killing of Y. Pseudotuberculosis–associated host cells results in engulfment by neighboring phagocytes of both bacteria and target cells, bypassing anti-phagocytosis. Our findings are consistent with a novel function for cell-mediated immune responses protecting against extracellular pathogens like Yersinia: perforin and CD8+ T cells are critical for hosts to overcome the anti-phagocytic action of Yops.
James B. Bliska - One of the best experts on this subject based on the ideXlab platform.
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effector cd8 t cells are generated in response to an immunodominant epitope in type iii effector yope during primary Yersinia Pseudotuberculosis Infection
Infection and Immunity, 2014Co-Authors: Yue Zhang, Patricio Mena, Galina Romanov, James B. BliskaAbstract:ABSTRACT YopE is a virulence factor that is secreted into host cells infected by Yersinia species. The YopE C-terminal domain has GTPase-activating protein (GAP) activity. The YopE N-terminal domain contains an epitope that is an immunodominant CD8 + T cell antigen during primary Infection of C57BL/6 mice with Yersinia Pseudotuberculosis. The characteristics of the CD8 + T cells generated in response to the epitope, which comprises YopE amino acid residues 69 to 77 (YopE 69–77 ), and the features of YopE that are important for antigenicity during primary Infection, are unknown. Following intravenous Infection of naive C57BL/6 mice with a yopE GAP mutant (the R144A mutant), flow cytometry analysis of splenocytes by tetramer and intracellular cytokine staining over a time course showed that YopE 69–77 -specific CD8 + T cells producing gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) were generated by day 7, with a peak at day 14. In addition, ∼80% of YopE 69–77 -specific CD8 + T cells were positive for KLRG1, a memory phenotype marker, at day 21. To determine if residues that regulate YopE activity by ubiquitination or membrane localization affect the antigenicity of YopE 69–77 , mice were infected with a yopE ubiquitination or membrane localization mutant (the R62K or L55N I59N L63N mutant, respectively). These mutants elicited YopE 69–77 -specific CD8 + T cells producing IFN-γ and TNF-α with kinetics and magnitudes similar to those of the parental R144A strain, indicating that primary Infection primes effector CD8 + T cells independently of the ubiquitination or membrane localization of YopE. Additionally, at day 7, there was an unexpected positive correlation between the numbers of YopE 69–77 -specific CD8 + T cells and CD11b + cells, but not between the numbers of YopE 69–77 -specific CD8 + T cells and bacterial cells, in spleens, suggesting that the innate immune response contributes to the immunodominance of YopE 69–77 .
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Comparison of YopE and YopT activities in counteracting host signalling responses to Yersinia Pseudotuberculosis Infection.
Cellular microbiology, 2006Co-Authors: Gloria I. Viboud, Edison Mejia, James B. BliskaAbstract:Pathogenic Yersinia species share a type III secretion system that translocates Yop effector proteins into host cells to counteract signalling responses during Infection. Two of these effectors, YopE and YopT, downregulate Rho GTPases by different mechanisms. Here, we investigate whether YopT and YopE are functionally redundant by dissecting the contribution of these two effectors to the pathogenesis of Yersinia Pseudotuberculosis in a mouse Infection and tissue culture model. Four days after oral Infection, a YopE(+) T (-) strain and a YopE(+) T (+) strain colonized spleens of mice at similar levels, suggesting that YopT is not required for virulence. In contrast, spleen colonization by a YopE(-)T(-) strain was significantly reduced. A YopE(-) T (+) strain colonized spleen at levels comparable to those of the YopE(+) T (-) strain, arguing that YopT can promote virulence in the absence of YopE. Infection of HeLa cells with a YopE(-) T(-)H(-)J(-) strain expressing either YopE or YopT showed that YopE had a stronger antiphagocytic activity than YopT. Expression of YopE strongly inhibited activation of JNK, ERK and NFkappaB, and prevented production of IL-8; whereas YopT moderately inhibited these responses. On the other hand, pore formation was inhibited equally by YopE or YopT. In conclusion, YopE is a potent inhibitor of Infection-induced signalling cascades, and YopT can only partially compensate for the loss of YopE.
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Inhibition of the Fc receptor-mediated oxidative burst in macrophages by the Yersinia Pseudotuberculosis tyrosine phosphatase.
Infection and immunity, 1995Co-Authors: James B. Bliska, D S BlackAbstract:Suppression of host-cell-mediated immunity is a hallmark feature of Yersinia Pseudotuberculosis Infection. To better understand this process, the interaction of Y. Pseudotuberculosis with macrophages and the effect of the virulence plasmid-encoded Yersinia tyrosine phosphatase (YopH) on the oxidative burst was analyzed in a chemiluminescence assay. An oxidative burst was generated upon Infection of macrophages with a plasmid-cured strain of Y. Pseudotuberculosis opsonized with immunoglobulin G antibody. Infection with plasmid-containing Y. Pseudotuberculosis inhibited the oxidative burst triggered by secondary Infection with opsonized bacteria. The tyrosine phosphatase activity of YopH was necessary for this inhibition. These results indicate that YopH inhibits Fc receptor-mediated signal transduction in macrophages in a global fashion. In addition, bacterial protein synthesis was not required for macrophage inhibition, suggesting that YopH export and translocation are controlled at the posttranslational level.
Ralph R Isberg - One of the best experts on this subject based on the ideXlab platform.
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community behavior and spatial regulation within a bacterial microcolony in deep tissue sites serves to protect against host attack
Cell Host & Microbe, 2015Co-Authors: Kimberly M Davis, Sina Mohammadi, Ralph R IsbergAbstract:Summary Bacterial pathogens express virulence-specific transcriptional programs that allow tissue colonization. Although phenotypic variation has been noted in the context of antibiotic exposure, no direct evidence exists for heterogeneity in virulence-specific transcriptional programs within tissues. In a mouse model of Yersinia Pseudotuberculosis Infection, we show that at least three subpopulations of bacteria develop within a single tissue site in response to distinct host signals. Bacteria growing on the exterior of spleen microcolonies responded to soluble signals and induced the nitric oxide (NO)-detoxifying gene, hmp . Hmp effectively eliminated NO diffusion and protected the interior bacterial population from exposure to NO-derived inducing signals. A third subpopulation, constituting the most peripherally localized bacteria, directly contacted neutrophils and transcriptionally upregulated a virulence factor. These studies demonstrate that growth within tissues results in transcriptional specialization within a single focus of microbial replication, facilitating directed pathogen counterattack against the host response.
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cd8 t cells restrict Yersinia Pseudotuberculosis Infection bypass of anti phagocytosis by targeting antigen presenting cells
PLOS Pathogens, 2009Co-Authors: Molly A. Bergman, Wendy P Loomis, Joan Mecsas, Michael N Starnbach, Ralph R IsbergAbstract:All Yersinia species target and bind to phagocytic cells, but uptake and destruction of bacteria are prevented by injection of anti-phagocytic Yop proteins into the host cell. Here we provide evidence that CD8+ T cells, which canonically eliminate intracellular pathogens, are important for restricting Yersinia, even though bacteria are primarily found in an extracellular locale during the course of disease. In a model of Infection with attenuated Y. Pseudotuberculosis, mice deficient for CD8+ T cells were more susceptible to Infection than immunocompetent mice. Although exposure to attenuated Y. Pseudotuberculosis generated TH1-type antibody responses and conferred protection against challenge with fully virulent bacteria, depletion of CD8+ T cells during challenge severely compromised protective immunity. Strikingly, mice lacking the T cell effector molecule perforin also succumbed to Y. Pseudotuberculosis Infection. Given that the function of perforin is to kill antigen-presenting cells, we reasoned that cell death marks bacteria-associated host cells for internalization by neighboring phagocytes, thus allowing ingestion and clearance of the attached bacteria. Supportive of this model, cytolytic T cell killing of Y. Pseudotuberculosis–associated host cells results in engulfment by neighboring phagocytes of both bacteria and target cells, bypassing anti-phagocytosis. Our findings are consistent with a novel function for cell-mediated immune responses protecting against extracellular pathogens like Yersinia: perforin and CD8+ T cells are critical for hosts to overcome the anti-phagocytic action of Yops.
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CD8(+) T cells restrict Yersinia Pseudotuberculosis Infection: bypass of anti-phagocytosis by targeting antigen-presenting cells.
PLoS pathogens, 2009Co-Authors: Molly A. Bergman, Wendy P Loomis, Joan Mecsas, Michael N Starnbach, Ralph R IsbergAbstract:All Yersinia species target and bind to phagocytic cells, but uptake and destruction of bacteria are prevented by injection of anti-phagocytic Yop proteins into the host cell. Here we provide evidence that CD8+ T cells, which canonically eliminate intracellular pathogens, are important for restricting Yersinia, even though bacteria are primarily found in an extracellular locale during the course of disease. In a model of Infection with attenuated Y. Pseudotuberculosis, mice deficient for CD8+ T cells were more susceptible to Infection than immunocompetent mice. Although exposure to attenuated Y. Pseudotuberculosis generated TH1-type antibody responses and conferred protection against challenge with fully virulent bacteria, depletion of CD8+ T cells during challenge severely compromised protective immunity. Strikingly, mice lacking the T cell effector molecule perforin also succumbed to Y. Pseudotuberculosis Infection. Given that the function of perforin is to kill antigen-presenting cells, we reasoned that cell death marks bacteria-associated host cells for internalization by neighboring phagocytes, thus allowing ingestion and clearance of the attached bacteria. Supportive of this model, cytolytic T cell killing of Y. Pseudotuberculosis–associated host cells results in engulfment by neighboring phagocytes of both bacteria and target cells, bypassing anti-phagocytosis. Our findings are consistent with a novel function for cell-mediated immune responses protecting against extracellular pathogens like Yersinia: perforin and CD8+ T cells are critical for hosts to overcome the anti-phagocytic action of Yops.
Helen Wang - One of the best experts on this subject based on the ideXlab platform.
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Spatiotemporal Variations in Growth Rate and Virulence Plasmid Copy Number during Yersinia Pseudotuberculosis Infection.
Infection and immunity, 2021Co-Authors: Stephan Schneiders, Tifaine Hechard, Tomas Edgren, Kemal Avican, Maria Fällman, Anna Fahlgren, Helen WangAbstract:Pathogenic Yersinia spp. depend on the activity of a potent virulence plasmid-encoded ysc/yop type 3 secretion system (T3SS) to colonize hosts and cause disease. It was recently shown that Y. Pseudotuberculosis up-regulates the virulence plasmid copy number (PCN) during Infection and the resulting elevated gene dose of plasmid-encoded T3SS genes is essential for virulence. When and how this novel regulatory mechanism is deployed and regulates the replication of the virulence plasmid during Infection is unknown. In the current study, we applied droplet digital PCR (ddPCR) to investigate the dynamics of Y. Pseudotuberculosis virulence PCN variations and growth rates in infected mouse organs. We demonstrated that both PCN and growth varied in different tissues and over time throughout the course of Infection, indicating that the bacteria adapted to discrete microenvironments during Infection. The PCN was highest in Peyer's Patches and caecum during the clonal invasive phase of the Infection, while the fastest growth rates were found in the draining mesenteric lymph nodes. In deeper, systemic organs, the PCN was lower and more modest growth rates were recorded. Our study indicates that increased gene dosage of the plasmid-encoded T3SS genes is most important early in the Infection during invasion of the host. The described ddPCR approach will greatly simplify analyses of PCN, growth dynamics, and bacterial loads in infected tissues, and will be readily applicable to other Infection models.
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Spatiotemporal Variations in Growth Rate and Virulence Plasmid Copy Number during Yersinia Pseudotuberculosis Infection
2020Co-Authors: Stephan Schneiders, Tifaine Hechard, Tomas Edgren, Kemal Avican, Maria Fällman, Anna Fahlgren, Helen WangAbstract:Pathogenic Yersinia spp. depend on the activity of a potent virulence plasmid-encoded ysc/yop type 3 secretion system (T3SS) to colonize hosts and cause disease. It was recently shown that Y. Pseudotuberculosis up-regulates the virulence plasmid copy number (PCN) during Infection and the resulting elevated gene dose of plasmid-encoded T3SS genes is essential for virulence. When and how this novel regulatory mechanism is deployed and regulates the replication of the virulence plasmid during Infection is unknown. In the current study, we applied droplet digital PCR (ddPCR) to investigate the dynamics of Y. Pseudotuberculosis virulence PCN variations and growth rates in infected mouse organs. We demonstrated that both PCN and growth varied in different tissues and over time throughout the course of Infection, indicating that the bacteria adapted to discrete microenvironments during Infection. The PCN was highest in Peyers Patches and caecum during the clonal invasive phase of the Infection, while the fastest growth rates were found in the draining mesenteric lymph nodes. In deeper, systemic organs, the PCN was lower and more modest growth rates were recorded. Our study indicates that increased gene dosage of the plasmid-encoded T3SS genes is most important early in the Infection during invasion of the host. The described ddPCR approach will greatly simplify analyses of PCN, growth dynamics, and bacterial loads in infected tissues, and will be readily applicable to other Infection models. ImportanceStudying pathogenic bacteria proliferating inside infected hosts is challenging using traditional methods, especially the transit and reversible genetic events. The bacteria are effectively diluted by the overwhelming number of host cells present in infected tissues. Using an innovative droplet digital PCR (ddPCR) approach, we have determined the virulence plasmid copy number (PCN) variations and growth rates of Yersinia during the course of Infection in a mouse model. Here, we show that both the virulence plasmid copy number and bacterial growth rates display spatiotemporal variations in mice during Infection. We demonstrate that the peak-to-trough ratio can be used as a proxy for determining the growth rate of invasive bacterial pathogen during Infection, and ddPCR as the method of choice for quantifying DNA in host-pathogen interaction context. This proof-of-concept ddPCR approach can be easily applied for any bacterial pathogens and any Infection models, for analysis of PCN, growth dynamics and bacterial loads.
