Transcriptome profile of Theileria infected bovine leucocytes under curcumin treatment
Ontology highlight
ABSTRACT:
ORGANISM(S): Theileria annulata Bos taurus
PROVIDER: GSE119138 | GEO | 2019/06/16
REPOSITORIES: GEO
Similar Datasets
Project description:Transcriptome profile of Theileria infected bovine leucocytes under curcumin treatment
| PRJNA488248 | ENA
Project description:To understand the immune response of cows to the apicomplexan parasite Theileria annulata, we used ex vivo isolate cells derived from two infected calve : Holstein 12886 (Bos taurus), which is known to be susceptible to the disease, and Sahiwal 82H (Bos indicus), which is known to be resistant. The infected bovine macrophages of the two species with Theileria were collected and performed multiome 10X Chromium genomics scRNA-Seq.
2024-10-09 | E-MTAB-14450 | biostudies-arrayexpress
Project description:The experiment investigates bovine gene expression in response to BW720c treatment in uninfected and Theileria annulata-infected cell cultures Theileria annulata, an intracellular parasite of bovine lymphoid cells, induces substantial phenotypic alterations to its host cell including continuous proliferation, cytoskeletal changes and resistance to apoptosis. While parasite induced modulation of host cell signal transduction pathways and NFκB activation are established, there remains considerable speculation on the complexities of the parasite directed control mechanisms that govern these radical changes to the host cell. Our objectives in this study were to provide a comprehensive analysis of the global changes to host cell gene expression with emphasis on those that result from direct intervention by the parasite. By using comparative microarray analysis of an uninfected bovine cell line and its Theileria infected counterpart, in conjunction with use of the specific parasitacidal agent, buparvaquone, we have identified a large number of host cell gene expression changes that result from parasite infection. Our results indicate that the viable parasite can irreversibly modify the transformed phenotype of a bovine cell line. 50% of genes with altered expression failed to show a reversible response to parasite death, a possible contributing factor to initiation of host cell apoptosis. The genes that did show an early predicted response to loss of parasite viability highlighted a sub-group of genes that are likely to be under direct control by parasite infection. Network and pathway analysis demonstrated that this sub-group is significantly enriched for genes involved in regulation of expression and chromatin modification. The results provide evidence that the Theileria parasite has the regulatory capacity to generate widespread change to host cell gene expression in a complex and reversible manner.
2013-07-04 | GSE44414 | GEO
Project description:The experiment investigates bovine gene expression in response to BW720c treatment in uninfected and Theileria annulata-infected cell cultures Theileria annulata, an intracellular parasite of bovine lymphoid cells, induces substantial phenotypic alterations to its host cell including continuous proliferation, cytoskeletal changes and resistance to apoptosis. While parasite induced modulation of host cell signal transduction pathways and NFκB activation are established, there remains considerable speculation on the complexities of the parasite directed control mechanisms that govern these radical changes to the host cell. Our objectives in this study were to provide a comprehensive analysis of the global changes to host cell gene expression with emphasis on those that result from direct intervention by the parasite. By using comparative microarray analysis of an uninfected bovine cell line and its Theileria infected counterpart, in conjunction with use of the specific parasitacidal agent, buparvaquone, we have identified a large number of host cell gene expression changes that result from parasite infection. Our results indicate that the viable parasite can irreversibly modify the transformed phenotype of a bovine cell line. 50% of genes with altered expression failed to show a reversible response to parasite death, a possible contributing factor to initiation of host cell apoptosis. The genes that did show an early predicted response to loss of parasite viability highlighted a sub-group of genes that are likely to be under direct control by parasite infection. Network and pathway analysis demonstrated that this sub-group is significantly enriched for genes involved in regulation of expression and chromatin modification. The results provide evidence that the Theileria parasite has the regulatory capacity to generate widespread change to host cell gene expression in a complex and reversible manner. Six experimental conditions with three replicates per condition. Total RNA prepared from cell cultures. BL20 (uninfected bovine lymphosarcoma cell line), BL20 24 hours post-BW720c treatment, BL20 48 hours post-BW720c, TBL (T. annulata infected bovine cell line), TBL 24 hours post-BW720c, TBL 48 hours post-BW720c. Each hydridisation represents bovine and parasite gene expression on a single channel and 2 technical replicates of each probeset are represented on the chip.
2013-07-04 | E-GEOD-44414 | biostudies-arrayexpress
Project description:We report significant changes in six bovine miRNA in vesicles from Theileria annulata infected cells
2019-05-14 | GSE118456 | GEO
Project description:Bovine tropical theileriosis is a tick-borne disease, caused by Theileria annulata which is a protozoan parasite that resides within the B-cells and macrophages. T. annulata is a unique parasite that can transform bovine leucocytes which leads to the cancer hallmarks in the infected cells. Previously, curcumin has been shown to possess multiple pharmacological activities such as anti-inflammatory and anti-cancer activities. In this study, we demonstrated that curcumin inhibits the proliferation of Theileria-transformed bovine leucocytes by promoting apoptosis and autophagy. The transcriptome analysis of curcumin treated cells showed that the genes involved in cell death and autophagy are also differentially regulated. We further elucidated the mechanism of action of curcumin on Theileria infected bovine cells. We found that curcumin induced the generation of reactive oxygen species (ROS) which activated caspase 8 and destabilized the mitochondrial membrane potential leading to the release of cytochrome c from mitochondria. This subsequently led to the activation of caspase 3 and PARP cleavage, finally leading to apoptosis in the infected cells. Furthermore, curcumin induced the process of autophagy which was characterized by the formation of acidic vesicular organelles, LC3B accumulation with lysosome inhibitor, E64d, and the presence of autophagosomes as visualized by transmission electron microscopy (TEM). Curcumin treatment suppressed the mTOR and increased the expression of autophagy-related proteins. We also found that N- acetylcysteine, an inhibitor of ROS, could rescue the infected cells from curcumin induced apoptosis and autophagy mediated cell death. Intriguingly, curcumin had no effect on uninfected bovine PBMCs. Altogether, these data suggest the therapeutic potential of curcumin against bovine tropical theileriosis.
| S-EPMC6547749 | biostudies-literature
Project description:Tropical theileriosis is a lymphoproliferative disease caused by the intracellular schizonts of Theileria annulata, an apicomplexan parasite. It causes severe infection in cattle and the untreated cattle would possibly die within 3-4 weeks of infection. The chemotherapy for this disease is largely dependent on the use of hydroxynaphthoquinone, namely buparvaquone. There have been reports recently of the development of resistance against this drug in T. annulata. Hence, identification of new drug molecule(s) or repurposing of existing drug molecule(s) against T. annulata is quite important. Here, we present the screening of 400 compounds included in the open-access Pathogen box from Medicine for Malaria Venture (MMV) to discover the novel compounds with potential inhibitory activity against T. annulata infected bovine leucocytes. We identified two compounds, MMV000062 and MMV560185, with IC50 values of 2.97 μM and 3.07 μM, respectively. MMV000062 and MMV560185 were found non-toxic to BoMac cells with CC50 values 34 μM and > 100 μM, respectively. The therapeutic indices of these compounds, MMV000062 and MMV560185, were calculated as more than 33 and 11, respectively. Further, it was observed that the parasite-infected cells under long-term culture were unable to recover with these compounds. We further deciphered that MMV560185 kills the infected cell by activation of TNFR-1 mediated extrinsic pathway of the apoptosis. The phenotypic characteristics of apoptosis were confirmed by Transmission Electron Microscopy. Our results suggest that it may be possible to develop MMV560185 further for chemotherapeutics of tropical theilerosis.
| S-EPMC8761611 | biostudies-literature
Project description:Intracellular pathogens develop elaborate mechanisms to survive within the hostile environments of host cells. Theileria parasites infect bovine leukocytes and cause devastating diseases in cattle in developing countries. Theileria spp. have evolved sophisticated strategies to hijack host leukocytes, inducing proliferative and invasive phenotypes characteristic of cell transformation. Intracellular Theileria parasites secrete proteins into the host cell and recruit host proteins to induce oncogenic signaling for parasite survival. It is unknown how Theileria parasites evade host cell defense mechanisms, such as autophagy, to survive within host cells. Here, we show that Theileria annulata parasites sequester the host eIF5A protein to their surface to escape elimination by autophagic processes. We identified a small-molecule compound that reduces parasite load by inducing autophagic flux in host leukocytes, thereby uncoupling Theileria parasite survival from host cell survival. We took a chemical genetics approach to show that this compound induced host autophagy mechanisms and the formation of autophagic structures via AMPK activation and the release of the host protein eIF5A which is sequestered at the parasite surface. The sequestration of host eIF5A to the parasite surface offers a strategy to escape elimination by autophagic mechanisms. These results show how intracellular pathogens can avoid host defense mechanisms and identify a new anti-Theileria drug that induces autophagy to target parasite removal.
2023-12-19 | GSE250088 | GEO
Project description:Theileria annulata is a tick-transmitted apicomplexan parasite that infects and transforms bovine leukocytes into disseminating tumors that cause a disease called tropical theileriosis. Using comparative transcriptomics we identified genes transcriptionally perturbed during Theileria-induced transformation and highlighted a small set of genes associated with leukocyte dissemination. CRISPR/Cas9-mediated knock-down of GZMA and RASGRP1 in macrophages attenuated for dissemination led to a regain in their dissemination in Rag2/gC mice confirming their suppressor roles in vivo. Comparing the transcriptomes of 934 human cancer cell lines to that of Theileria-transformed bovine B cells again highlighted GZMA and RASGRP1 and CRISPR-mediated overexpression of GZMA and RASGRP1 dampened the dissemination potential of human B-lymphomas. The ensemble provide evidence for a novel suppressor function in the dissemination of both T. annulata-transformed bovine leukocytes and human B-lymphomas.
2020-08-18 | GSE135377 | GEO
Project description:The experiment investigates bovine gene expression in response to LPS in uninfected and Theileria annulata-infected cell cultures A subset of genes are identified which are activated in response to LPS stimulation with further modulation due to parasite infection.
2012-10-01 | GSE36428 | GEO