Submandibular lymph node, a key battleground for host-Yersinia pestis interaction: A transcriptomic study using non-human primate model
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PROVIDER: PRJNA395085 | ENA |
REPOSITORIES: ENA
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Project description:Initiation of treatment during the pre-symptomatic phase of infection with Yersinia pestis (Y. pestis) is particularly critical because the rapid proliferation of Y. pestis is coupled with the manifestation of common flu-like early symptoms that often delay the intervention. Our study used African Green Monkeys that didn’t exhibited clear clinical symptoms for nearly two days after intranasal challenge with Y. pestis and succumbed within a day after showing the first signs of clinical discomfort. Colonization of Y. pestis was detected in blood one day post-infection although blood transcripts were found to be altered immediately after the pathogenic assault. The organs of the respiratory tract and those adjacent, such as lungs and submandibular lymph nodes, accumulated significant Y. pestis colonization immediately after pathogenic challenge. Hence organ-specific molecular investigations are deemed to be the key in elucidation of the mechanisms of the initial host response. Based on results from our previous investigation of the blood transcriptomic profile, we explored the early involvement of the ubiquitin-microtubule-mediated host defense mechanism in detail. Genes enriching the ubiquitin network were altered, indicating an early suppression of the network functions in the submandibular lymph nodes. In concert, the upstream toll-like receptor signaling and downstream IκB kinase/NFκB signaling were inhibited at the transcription level. The inflammatory response was suppressed in the lungs, submandibular lymph nodes and mediastinal lymph nodes. By dysregulating both ubiquitin and the microtubule networks, Yersinia pestis was able to impair host-mediated proteolysis activities and evade autophagosome capture. A synchronized suppression of the immune response may render the peripheral organs more vulnerable to the imminent pathogenic assault. Furthermore, a comprehensive early onset of apoptosis was found across these three organ types. This was possibly a parallel mechanism undertaken by Yersinia pestis to further weaken the host response and enable a permissive colonization of the host. Targeting these networks in an organ-specific and time-resolved fashion could be essential for development of the next generation therapeutics for pneumonic plague.
2017-10-31 | GSE101653 | GEO
Project description:The process of metastasis starts even before the tumor cells actually metastasize to the lymph nodes. In this study, mice were injected with B16-F10 murine melanoma cells to generate a tongue submandibular lymph node (SLN) metastasis model in which to investigate genes of interest.
2022-02-23 | GSE197190 | GEO
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: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:In this study, we analyzed the submandibular glands of P40-/-CD25+/- (control mice) and P40-/-CD25-/- (SS mice) after PD-1-targeted CAR-T cells or control T cells treatment using RNA-Seq. We found that the transcription of inflammatory genes was down-regulated and the transcription of tissue repair genes was up-regulated in the submandibular glands of SS mice after PD-1-targeted CAR-T cells treatment. In addition, PD-1+Tigit+CD8+ T cells in the submandibular gland draining lymph nodes of SS mice showed transcription characteristics of tissue resident memory precursors.
2024-12-15 | GSE253818 | GEO
Project description:Single-cell RNA-sequencing of porcine submandibular lymph node cells from ASF-immune and nonimmune pigs
| PRJNA805107 | ENA
Project description:Yersinia pestis causes bubonic plague in humans and rats. The disease is characterized by an enlarged, painful lymph node, termed a bubo, that develops following bacterial dissemination from an intradermal flea bite injection site. In susceptible animals, the bacteria quickly overcome host innate immune defenses in the lymph node, spread systemically through the blood, and produce fatal sepsis 1,2. At the terminal stage of disease, the bubo contains massive numbers of extracellular bacteria, necrotic lymphoid tissue, hemorrhage, and fibrin 2. The extreme virulence of Y. pestis has been largely ascribed to its ability to avoid innate immunity by preventing phagocytosis, selectively killing immune cells, and down regulating the proinflammatory response 3. Here we report that two innate immune effector mechanisms are generated during bubonic plague in the rat: iron limitation and nitrosative stress. The expression of nitric oxide synthase (iNOS) by rat polymorphonuclear neutrophils (PMNs) was induced in the bubo, and mutation of the Y. pestis hmp gene, which encodes a flavohemoglobin important for resistance to nitric oxide (NO), attenuated virulence. Thus, although Y. pestis avoids uptake and intracellular killing by phagocytes, it still encounters innate immune effector molecules, particularly phagocyte-derived reactive nitrogen species, in the extracellular environment of the bubo. Keywords: repeat
2006-07-28 | GSE3793 | GEO
Project description:In this study we focussed our investigations on ECM remodelling by FRCs during lymph node (LN) expansion, and the interconnection between the cellular and ECM components of the conduit network. We demonstrate a loss of ECM components of the conduit during acute LN expansion
2021-05-11 | PXD015816 | Pride
Project description:Familial Blood and Lymph Node Cancers
| PRJNA344002 | ENA