Similar Datasets
Project description:Pneumonic plague is the most deadly form of infection caused by Yersinia pestis and can progress extremely fast. However, our understanding on the host transcriptomic response to pneumonic plague is insufficient. Here, we used RNA-sequencing technology to analyze transcriptomic responses in mice infected with fully virulent strain 201 or EV76, a live attenuated vaccine strain lacking the pigmentation locus. Approximately 600 differentially expressed genes (DEGs) were detected in lungs from both 201- and EV76-infected mice at 12 hours post-infection (hpi). DEGs in lungs of 201-infected mice exceeded 2,000 at 48 hpi, accompanied by sustained large numbers of DEGs in the liver and spleen; however, limited DEGs were detected in those organs of EV-infected mice. Remarkably, DEGs in lungs were significantly enriched in critical immune responses pathways in EV76-infected but not 201-infected mice, including antigen processing and presentation, T cell receptor signaling among others. Pathological and bacterial load analyses confirmed the rapid systemic dissemination of 201-infection and the confined EV76-infection in lungs. Our results demonstrate that fully virulent Y. pestis strongly inhibits both the innate and adaptive immune responses that are substantially stimulated in a self-limited infection, which update our holistic views on the transcriptomic response to pneumonic plague.
2017-07-13 | GSE84341 | GEO
Project description:During pneumonic plague, the bacterium Yersinia pestis elicits the development of inflammatory lung lesions that continue to expand throughout infection. This lesion development and persistence is poorly understood. Here, we examine spatially distinct regions of lung lesions using laser capture microdissection and RNAseq analysis to identify transcriptional differences between lesion microenvironments. We show that cellular pathways involved in leukocyte migration and apoptosis are down regulated in the center of lung lesions compared to the periphery. Probing for the bacterial factor(s) important for the alteration in neutrophil survival, we show both in vitro and in vivo that Y. pestis increases neutrophil survival in a manner that is dependent on the type-III secretion system effector YopM. This research explores the complexity of spatially distinct host - microbe interactions and emphasizes the importance of cell relevance in assays in order to fully understand Y. pestis virulence.
2015-07-13 | GSE70819 | GEO
Project description:Although pneumonic plague is the deadliest manifestation of disease caused by the bacterium Yersinia pestis, there is surprisingly little information on the cellular and molecular mechanisms responsible for Y. pestis-triggered pathology in the lung. Therefore, to understand the progression of this unique disease, we developed an intranasal mouse model of primary pneumonic plague. Mice succumbed to a purulent multifocal severe exudative bronchopneumonia that closely resembles the disease observed in humans. In order to assess the adaptation of Y. pestis to a mammalian environment, we employed DNA microarray technology to analyze the transcriptional responses of the bacteria during interaction with the mouse lung as compared to bacteria cultured in vitro. Keywords: Infectious expression analysis
2005-11-10 | GSE3575 | GEO
Project description:During pneumonic plague, the bacterium Yersinia pestis elicits the development of inflammatory lung lesions that continue to expand throughout infection. This lesion development and persistence is poorly understood. Here, we examine spatially distinct regions of lung lesions using laser capture microdissection and RNAseq analysis to identify transcriptional differences between lesion microenvironments. We show that cellular pathways involved in leukocyte migration and apoptosis are down regulated in the center of lung lesions compared to the periphery. Probing for the bacterial factor(s) important for the alteration in neutrophil survival, we show both in vitro and in vivo that Y. pestis increases neutrophil survival in a manner that is dependent on the type-III secretion system effector YopM. This research explores the complexity of spatially distinct host - microbe interactions and emphasizes the importance of cell relevance in assays in order to fully understand Y. pestis virulence. We examine spatially distinct regions of lung lesions using laser capture microdissection and RNAseq analysis to identify transcriptional differences between lesion microenvironments. Sample types: uninfected BM-PMN, infected BM-PMN, lesion periphery, lesion center.
2015-07-13 | E-GEOD-70819 | biostudies-arrayexpress
Project description:transcriptomic analyses showed there was a very rapid proliferation of Y. pestis in assault on African green monkeys. The bacterial loads were enumerated in the blood at delayed time points supporting earlier observations (Layton et al., 2011). Interpretation of transcriptomic changes reveals that the host defense has been essentially shattered, and the process of multi-organ failure was initiated one day after inhalation exposure. At 24 h post-exposure, the diseased animals were possibly at the middle of their survival curves. Hence, such molecular indicators could have critical therapeutic values, particularly when therapies fail to intervene at the earliest opportunity. In the early phase of pathogenesis, systematic reprogramming of both adaptive and innate immunity programs is mediated, leading to sepsis. Results suggest the possibility of early molecular perturbations in the lungs and muscle tissues, and catabolic related activities, such as biosynthesis. Apoptosis ensued at the early stage, which potentially became rapid by recruiting an increasing number of apoptotic networks. Beyond 24 h, rapid apoptosis could have acted in concert with hypercytokinemia and hyperchemokinemia, resulting in failures of many peripheral organs. Following a published report (Layton et al., 2011), the present study was designed to expose the nonhuman primates with a target dose of 100 ± 50 ED50 aerosolized Y. pestis strain CO92 under ABSL-3 conditions. Seventy-two hours prior to aerosol exposure, all animals were moved into the ABSL-3 for acclimatization. As described in Figure S1, initial blood draws were carried out 24 h before Y. pestis aerosol challenge. The animals were challenged via aerosol with 1 x 106 virulent organisms while under anesthesia with 4 mg/kg Telazol (Fort Dodge Animal Health, Fort Dodge, IA). Post-exposure clinical illness and disseminated infection were evaluated by direct clinical observations. All animals within each group were exposed on the same day at 30 minute intervals, and subsequent blood draws were conducted at 45 m, 6 h, 9 h, 12 h, 18 h, 24 h, 32 h and 42 h.
2016-01-14 | E-GEOD-63560 | biostudies-arrayexpress
Project description:Purpose: In previous studies, we found that the fyuA gene plays an important role in the virulence and pathogenicity of Yersinia pestis strain 201. In order to globally observe which functions of the fyuA gene also affect Y. pestis, we performed RNA-seq on the Y. pestis wild strain 201-WT and mutant strains △fyuA and △fyuAGCAdel, hoping to find their differences at the transcription level, so that better elucidate the effect of fyuA gene on Y. pestis gene transcription. Methods: Total RNA was extracted using the PureLink™ RNA Mini Kit, and then used for creating a cDNA library and deep sequencing. According to the values of Fragments Per Kilobase of Transcript per Million Mapped Reads (FPKM), the ratio of transcript levels between WT and ΔfyuAGCAdel groups was used as the logarithm to the base 2 (twofold change). The differential values of at least a 2-fold were applied to analyze the differential expression of genes according to the Y. pestis 91001 genome annotation. The transcriptome data were verified by qPCR. Results: We found that compared with 201-WT, genes related to siderophore synthesis such as ybtS, ybtX, ybtQ, irp2, irp1, ybtU, ybtT and ybtE were significantly down-regulated at either 26 ℃ or 37 ℃. At 37 ℃, the genes related to type Ⅲ secretion system were significantly up-regulated.
2022-03-22 | GSE198937 | GEO
Project description:Transcriptome Profiling Reveals the Progression of Primary Pneumonic Plague
| PRJNA908829 | ENA
Project description:A delay in the mammalian inflammatory response is a prominent feature of infection with Yersinia pestis, the agent of bubonic and pneumonic plague. Y. pestis factors have been identified that either do not stimulate a normal inflammatory response, or actively suppress it. Prominent among these are components of the Type III secretion system that is encoded on the Yersinia virulence plasmid (pYV). We used a rat model of bubonic plague to characterize the kinetics and extent of the mammalian transcriptomic response to infection with wild-type or pYV-negative Y. pestis in the draining lymph node. Remarkably, dissemination and multiplication of wild-type Y. pestis during the bubonic stage of disease did not induce any detectable gene expression response by host lymph node cells. This was followed, however, by an extensive transcriptomic response, including upregulation of several cytokine, chemokine, and other immune response genes, after systemic spread during septicemic plague. Matched lymph node samples used for histopathology and extracellular cytokine measurements, combined with the microarray data set, broadly outlined the mammalian immune response to Y. pestis and how it is influenced by pYV-encoded factors. The results indicate that both WT and pYV– Y. pestis induce primarily a Th17 response, and not a Th1 or Th2 response. In the absence of pYV, a sustained recruitment of polymorphonuclear leukocytes, the major Th17 effector cell, to the lymph node resulted in clearance of infection. Thus, the ability to counteract a Th17- driven PMN response in the lymph node appears to be a major function of the Y. pestis virulence plasmid. In contrast, classic markers of the proinflammatory response and macrophage activation, such as TNF-á and IFN-ã, were not induced at all by pYV– Y. pestis, and appeared only late in infection with WT Y. pestis. Rats treated with PBS and Yersinia pestis at various time points.
2010-12-07 | E-GEOD-22299 | biostudies-arrayexpress
Project description:A delay in the mammalian inflammatory response is a prominent feature of infection with Yersinia pestis, the agent of bubonic and pneumonic plague. Y. pestis factors have been identified that either do not stimulate a normal inflammatory response, or actively suppress it. Prominent among these are components of the Type III secretion system that is encoded on the Yersinia virulence plasmid (pYV). We used a rat model of bubonic plague to characterize the kinetics and extent of the mammalian transcriptomic response to infection with wild-type or pYV-negative Y. pestis in the draining lymph node. Remarkably, dissemination and multiplication of wild-type Y. pestis during the bubonic stage of disease did not induce any detectable gene expression response by host lymph node cells. This was followed, however, by an extensive transcriptomic response, including upregulation of several cytokine, chemokine, and other immune response genes, after systemic spread during septicemic plague. Matched lymph node samples used for histopathology and extracellular cytokine measurements, combined with the microarray data set, broadly outlined the mammalian immune response to Y. pestis and how it is influenced by pYV-encoded factors. The results indicate that both WT and pYV– Y. pestis induce primarily a Th17 response, and not a Th1 or Th2 response. In the absence of pYV, a sustained recruitment of polymorphonuclear leukocytes, the major Th17 effector cell, to the lymph node resulted in clearance of infection. Thus, the ability to counteract a Th17- driven PMN response in the lymph node appears to be a major function of the Y. pestis virulence plasmid. In contrast, classic markers of the proinflammatory response and macrophage activation, such as TNF-á and IFN-ã, were not induced at all by pYV– Y. pestis, and appeared only late in infection with WT Y. pestis.
2010-12-07 | GSE22299 | GEO
Project description:Many pathogens usurp the host hemostatic system during infection to promote pathogenesis. Yersinia pestis, the causative agent of plague, expresses the plasminogen activator protease Pla, which has been shown in vitro to target and cleave multiple proteins within the fibrinolytic pathway, including the plasmin inhibitor ?2-antiplasmin (A2AP). It is not known, however, if Pla inactivates A2AP in vivo; the role of A2AP during respiratory Y. pestis infection is not known either. Here, we show that Y. pestis does not appreciably cleave A2AP in a Pla-dependent manner in the lungs during experimental pneumonic plague. Furthermore, following intranasal infection with Y. pestis, A2AP-deficient mice exhibit no difference in survival time, bacterial burden in the lungs, or dissemination from wild-type mice. Instead, we found that in the absence of Pla, A2AP contributes to the control of the pulmonary inflammatory response during infection by reducing neutrophil recruitment and cytokine production, resulting in altered immunopathology of the lungs compared to A2AP-deficient mice. Thus, our data demonstrate that A2AP is not significantly affected by the Pla protease during pneumonic plague, and although A2AP participates in immune modulation in the lungs, it has limited impact on the course or ultimate outcome of the infection.
| S-EPMC4645379 | biostudies-literature