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  • 1
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    Online Resource
    Dual transcriptomics to decipher the interferon-gamma independent responses to intestinal Cryptosporidium parvum infection.
    The American Association of Immunologists ; 2021
    In:  The Journal of Immunology Vol. 206, No. 1_Supplement ( 2021-05-01), p. 16.25-16.25
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 206, No. 1_Supplement ( 2021-05-01), p. 16.25-16.25
    Abstract: This study characterizes the IFNγ independent host immune response against C. parvum to discover new targets to halt the disease. We used transcriptomic analysis of ileum and cecum intestinal sections of IFNγ-deleted mice that were treated with Soluble Toxoplasma gondii antigen (STAg) or PBS upon C. parvum infection. Results: STAg treatment reduced the oocyst shedding in C. parvum infected IFNγ deleted mice. To understand the IFNγ independent mechanism of STAg treatment against C. parvum, we performed 12 RNAseq comparisons between tissues, treatments, and infection status for Mus musculus and C. parvum. In the ileum, regardless of STAg or PBS treatment, more than 100 genes had a significant differential expression. Within STAg treated mice, a total of 129 genes for ileum and 78 for the cecum were classified as differentially expressed. We found in high abundance at least 28 genes related to IFN type I response in infected mice treated with STAg, among them, the oligoadenylate synthetase and Schlafen family gene members. For C. parvum transcriptome analysis, we observed in the ileum high abundance of the oocyst wall protein 1 and some mucins; while in the cecum, the RRM domain containing-protein and Tryptophan synthase beta chain transcripts were the more abundant transcripts. Conclusions: STAg treatment and C. parvum infection induced a type I interferon response that would be the cause of the reduction of oocyst shedding in STAG treated mice in an IFNy independent manner. While the depth of sequence did not allow us to observe in detail differential expression of genes in C. parvum, we found differences in parasite gene expression between the ileum and the cecum.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.206.Supp.16.25
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2021
    detail.hit.zdb_id: 1475085-5
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  • 2
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    Using Entamoeba muris To Model Fecal-Oral Transmission of Entamoeba in Mice
    American Society for Microbiology ; 2023
    In:  mBio Vol. 14, No. 1 ( 2023-02-28)
    Details
    In: mBio, American Society for Microbiology, Vol. 14, No. 1 ( 2023-02-28)
    Abstract: There are several Entamoeba species that colonize humans, but only Entamoeba histolytica causes severe disease. E. histolytica is transmitted through the fecal-oral route to colonize the intestinal tract of 50 million people worldwide. The current mouse model to study E. histolytica intestinal infection directly delivers the parasite into the surgically exposed cecum, which circumvents the natural route of infection. To develop a fecal-oral mouse model, we screened our vivarium for a natural murine Entamoeba colonizer via a pan- Entamoeba PCR targeting the 18S ribosomal gene. We determined that C57BL/6 mice were chronically colonized by Entamoeba muris. This amoeba is closely related to E. histolytica , as determined by 18S sequencing and cross-reactivity with an E. histolytica -specific antibody. In contrast, outbred Swiss Webster (SW) mice were not chronically colonized by E. muris. We orally challenged SW mice with 1 × 10 5 E. muris cysts and discovered they were susceptible to infection, with peak cyst shedding occurring between 5 and 7 days postinfection. Most infected SW mice did not lose weight significantly but trended toward decreased weight gain throughout the experiment compared to mock-infected controls. Infected mice treated with paromomycin, an antibiotic used against noninvasive intestinal disease, do not become colonized by E. muris . Within the intestinal tract, E. muris localizes exclusively to the cecum and colon. Purified E. muris cysts treated with bovine bile in vitro excyst into mobile, pretrophozoite stages. Overall, this work describes a novel fecal-oral mouse model for the important global pathogen E. histolytica . IMPORTANCE Infection with parasites from the Entamoeba genus are significantly underreported causes of diarrheal disease that disproportionally impact tropical regions. There are several species of Entamoeba that infect humans to cause a range of symptoms from asymptomatic colonization of the intestinal tract to invasive disease with dissemination. All Entamoeba species are spread via the fecal-oral route in contaminated food and water. Studying the life cycle of Entamoeba , from host colonization to infectious fecal cyst production, can provide targets for vaccine and drug development. Because there is not an oral challenge rodent model, we screened for a mouse Entamoeba species and identified Entamoeba muris as a natural colonizer. We determine the peak of infection after an oral challenge, the efficacy of paromomycin treatment, the intestinal tract localization, and the cues that trigger excystation. This oral infection mouse model will be valuable for the development of novel therapeutic options for Entamoeba infections.
    Type of Medium: Online Resource
    ISSN: 2150-7511
    URL: Article
    DOI: 10.1128/mbio.03008-22
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2023
    detail.hit.zdb_id: 2557172-2
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  • 3
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    Entamoeba histolytica: Five facts about modeling a complex human disease in rodents
    Public Library of Science (PLoS) ; 2020
    In:  PLOS Pathogens Vol. 16, No. 11 ( 2020-11-12), p. e1008950-
    Details
    In: PLOS Pathogens, Public Library of Science (PLoS), Vol. 16, No. 11 ( 2020-11-12), p. e1008950-
    Type of Medium: Online Resource
    ISSN: 1553-7374
    URL: Article
    URL: Article
    DOI: 10.1371/journal.ppat.1008950
    DOI: 10.1371/journal.ppat.1008950.g001
    Language: English
    Publisher: Public Library of Science (PLoS)
    Publication Date: 2020
    detail.hit.zdb_id: 2205412-1
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  • 4
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    Dual Transcriptomics To Determine Gamma Interferon-Independent Host Response to Intestinal Cryptosporidium parvum Infection
    American Society for Microbiology ; 2022
    In:  Infection and Immunity Vol. 90, No. 2 ( 2022-02-17)
    Details
    In: Infection and Immunity, American Society for Microbiology, Vol. 90, No. 2 ( 2022-02-17)
    Abstract: Animals with a chronic infection of the parasite Toxoplasma gondii are protected against lethal secondary infection with other pathogens. Our group previously determined that soluble T. gondii antigens (STAg) can mimic this protection and be used as a treatment against several lethal pathogens. Because treatments are limited for the parasite Cryptosporidium parvum , we tested STAg as a C. parvum therapeutic. We determined that STAg treatment reduced C. parvum Iowa II oocyst shedding in gamma interferon knockout (IFN-γ-KO) mice. Murine intestinal sections were then sequenced to define the IFN-γ-independent transcriptomic response to C. parvum infection. Gene Ontology and transcript abundance comparisons showed host immune response and metabolism changes. Transcripts for type I interferon-responsive genes were more abundant in C. parvum -infected mice treated with STAg. Comparisons between phosphate-buffered saline (PBS) and STAg treatments showed no significant differences in C. parvum gene expression. C. parvum transcript abundance was highest in the ileum and mucin-like glycoproteins and the GDP-fucose transporter were among the most abundant. These results will assist the field in determining both host- and parasite-directed future therapeutic targets.
    Type of Medium: Online Resource
    ISSN: 0019-9567 , 1098-5522
    URL: Article
    DOI: 10.1128/iai.00638-21
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 1483247-1
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  • 5
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    Online Resource
    A Toxoplasma gondii lipoxygenase-like enzyme is necessary for virulence and changes localization associated with the host immune response
    American Society for Microbiology ; 2023
    In:  mBio
    Details
    In: mBio, American Society for Microbiology
    Abstract: Lipoxygenases (LOXs) are enzymes that catalyze the deoxygenation of polyunsaturated fatty acids such as linoleic and arachidonic acid. These modifications create signaling molecules that are best characterized for modulating the immune response. Deletion of the first lipoxygenase-like enzyme characterized for Toxoplasma gondii (TgLOXL1) generated a less virulent strain, and infected mice showed a decreased immune response. This virulence defect was dependent on the mouse cytokine interferon gamma IFNγ. TgLOXL1 changes location from inside the parasite in tissue culture conditions to vesicular structures within the host immune cells during mouse infection. These results suggest that TgLOXL1 plays a role in the modification of the host immune response in mice.
    Type of Medium: Online Resource
    ISSN: 2150-7511
    URL: Article
    DOI: 10.1128/mbio.01279-23
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2023
    detail.hit.zdb_id: 2557172-2
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