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  • American Society for Microbiology  (3)
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  • American Society for Microbiology  (3)
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  • 1
    Online Resource
    Online Resource
    Single-Cell RNA Sequencing Reveals the Heterogeneity of Infiltrating Immune Cell Profiles in the Hepatic Cystic Echinococcosis Microenvironment
    American Society for Microbiology ; 2021
    In:  Infection and Immunity Vol. 89, No. 12 ( 2021-11-16)
    Details
    In: Infection and Immunity, American Society for Microbiology, Vol. 89, No. 12 ( 2021-11-16)
    Abstract: Human cystic echinococcosis, caused by the larval stage of Echinococcus granulosus sensu lato , has been reported a near-cosmopolitan zoonotic disease. Various infiltrating immune cells gather around the lesion and produce a lesion microenvironment; however, cellular composition and heterogeneity in hepatic cystic echinococcosis lesion microenvironments are incompletely understood. Here, 81,865 immune cells isolated from peripheral blood, perilesion liver tissue, and adjacent normal liver tissue from four cystic echinococcosis patients were profiled using single-cell RNA sequencing. We identified 23 discrete cell populations and found distinct differences in infiltrating immune cells between tissue environments. Despite the significant similarity between perilesion and adjacent normal liver tissue-resident immune cells, the cellular proportions of type 2 innate lymphoid cells (ILC2s) and plasmacytoid dendritic cells (pDCs) were higher in perilesion liver tissue. Interestingly, the immunosuppressive gene NFKBIA was upregulated in these cells. Seven subsets of CD4 + T cell populations were found, and there were more regulatory-CD4 + T cells (Treg-CD4 + ) and Th2-CD4 + T cells in perilesion tissue than in adjacent normal tissue. There was close contact between CD4 + T cells and ILC2s and pDCs, which caused upregulation of genes related to positive immune activity in adjacent normal liver tissue. However, expression of genes related to immunosuppression, especially the immune inhibitory checkpoint gene NKG2A / HLA-E , was obviously higher in perilesion tissue, suggesting that cellular interaction resulted in an inhibitory microenvironment in the cystic echinococcosis (CE) lesion. This work offers new insights into the transcriptional heterogeneity of infiltrating immune cells in hepatic cystic echinococcosis lesion microenvironments at a single-cell level and provides potential target signatures for diagnosis and immunotherapies.
    Type of Medium: Online Resource
    ISSN: 0019-9567 , 1098-5522
    URL: Article
    DOI: 10.1128/IAI.00297-21
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2021
    detail.hit.zdb_id: 1483247-1
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Single-Cell Heterogeneity of the Liver-Infiltrating Lymphocytes in Individuals with Chronic Echinococcus multilocularis Infection
    American Society for Microbiology ; 2022
    In:  Infection and Immunity Vol. 90, No. 11 ( 2022-11-17)
    Details
    In: Infection and Immunity, American Society for Microbiology, Vol. 90, No. 11 ( 2022-11-17)
    Abstract: Human alveolar echinococcosis (AE) is a tumor-like disease predominantly located in the liver. The cellular composition and heterogeneity of the lesion-infiltrating lymphocytes which produce an “immunosuppressive” microenvironment are poorly understood. Here, we profiled 83,921 CD45 + lymphocytes isolated from the peripheral blood (PB), perilesion (PL), and adjacent normal (AN) liver tissue of four advanced-stage AE patients using single-cell RNA and T-cell receptor (TCR) sequencing technology. We identified 23 large clusters, and the distributions and transcriptomes of these cell clusters in the liver and periphery were different. The cellular proportions of exhausted CD8 + T cells and group 2 innate lymphoid cells (ILC2s) were notably higher in PL tissue, and the expression features of these cell subsets were related to neoplasm metastasis and immune response suppression. In the 5 CD8 + T-cell populations, only CD8 + mucosa-associated invariant T (MAIT) cells were enriched in PL samples and the TRAV1-2_TRAJ33_TRAC TCR was clonally expanded. In the 11 subsets of CD4 + T cells, Th17 cells and induced regulatory T cells (iTregs) were preferentially enriched in PL samples, and their highly expressed genes were related to cell invasion, tumor metastasis, and inhibition of the inflammatory immune response. Exhaustion-specific genes (TIGIT, PD-1, and CTLA4) were upregulated in Tregs. Interestingly, there was a close contact between CD8 + T cells and iTregs or Th17 cells, especially for genes related to immunosuppression, such as PDCD1-FAM3C, which were highly expressed in PL tissue. This transcriptional data set provides valuable insights and a rich resource for deeply understanding the immune microenvironment in AE, which could provide potential target signatures for AE diagnosis and immunotherapies.
    Type of Medium: Online Resource
    ISSN: 0019-9567 , 1098-5522
    URL: Article
    DOI: 10.1128/iai.00177-22
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 1483247-1
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    Online Resource
  • 3
    Online Resource
    Online Resource
    Identification of Functional MKK3/6 and MEK1/2 Homologs from Echinococcus granulosus and Investigation of Protoscolecidal Activity of Mitogen-Activated Protein Kinase Signaling Pathway Inhibitors In Vitro and In Vivo
    American Society for Microbiology ; 2019
    In:  Antimicrobial Agents and Chemotherapy Vol. 63, No. 1 ( 2019-01)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 63, No. 1 ( 2019-01)
    Abstract: Cystic echinococcosis is a zoonosis caused by the larval stage of Echinococcus granulosus sensu lato . There is an urgent need to develop new drugs for the treatment of this disease. In this study, we identified two new members of mitogen-activated protein kinase (MAPK) cascades, MKK3/6 and MEK1/2 homologs (termed EgMKK1 and EgMKK2, respectively), from E. granulosus sensu stricto . Both EgMKK1 and EgMKK2 were expressed at the larval stages. As shown by yeast two-hybrid and coimmunoprecipitation analyses, EgMKK1 interacted with the previously identified Egp38 protein but not with EgERK. EgMKK2, on the other hand, interacted with EgERK. In addition, EgMKK1 and EgMKK2 displayed kinase activity toward the substrate myelin basic protein. When sorafenib tosylate, PD184352, or U0126-ethanol (EtOH) was added to the medium for in vitro culture of E. granulosus protoscoleces (PSCs) or cysts, an inhibitory and cytolytic effect was observed via suppressed phosphorylation of EgMKKs and EgERK. Nonviability of PSCs treated with sorafenib tosylate or U0126-EtOH, and not with PD184352, was confirmed through bioassays, i.e., inoculation of treated and untreated protoscoleces into mice. In vivo treatment of E. granulosus sensu stricto -infected mice with sorafenib tosylate or U0126-EtOH for 4 weeks demonstrated a reduction in parasite weight, but the results did not show a significant difference. In conclusion, the MAPK cascades were identified as new targets for drug development, and E. granulosus was efficiently inhibited by their inhibitors in vitro . The translation of these findings into in vivo efficacy requires further adjustment of treatment regimens using sorafenib tosylate or, possibly, other kinase inhibitors.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.01043-18
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2019
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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