ROP18-Mediated Transcriptional Reprogramming of HEK293T Cell Reveals New Roles of ROP18 in the Interplay Between Toxoplasma gondii and the Host Cell

Li, Jiexi; He, Jun-Jun; Elsheikha, Hany M.; Ma, Jun; Xu, Xiaoqing; Zhu, Xingquan

doi:10.3389/fcimb.2020.586946

Cited by 8 publications

(4 citation statements)

References 86 publications

(95 reference statements)

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“…Other host processes may then be easier to interfere with and hijacked by T. gondii . The results of the present and previous studies [ 30 , 31 , 32 , 33 , 34 , 35 ], confirm the ability of T. gondii to manipulate various cellular processes, particularly immune response via reprogramming host gene expression to support its own survival within the host cells.…”

Section: Discussionsupporting

confidence: 88%

Illuminating Host-Parasite Interaction at the Cellular and Subcellular Levels with Infrared Microspectroscopy

Elsheikha

Al-sandaqchi

Harun

et al. 2022

Cells

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Toxoplasma gondii (T. gondii) is an opportunistic protozoan that can cause brain infection and other serious health consequences in immuno-compromised individuals. This parasite has a remarkable ability to cross biological barriers and exploit the host cell microenvironment to support its own survival and growth. Recent advances in label-free spectroscopic imaging techniques have made it possible to study biological systems at a high spatial resolution. In this study, we used conventional Fourier-transform infrared (FTIR) microspectroscopy and synchrotron-based FTIR microspectroscopy to analyze the chemical changes that are associated with infection of human brain microvascular endothelial cells (hBMECs) by T. gondii (RH) tachyzoites. Both FTIR microspectroscopic methods showed utility in revealing the chemical alterations in the infected hBMECs. Using a ZnS hemisphere device, to increase the numerical aperture, and the synchrotron source to increase the brightness, we obtained spatially resolved spectra from within a single cell. The spectra extracted from the nucleus and cytosol containing the tachyzoites were clearly distinguished. RNA sequencing analysis of T. gondii-infected and uninfected hBMECs revealed significant changes in the expression of host cell genes and pathways in response to T. gondii infection. These FTIR spectroscopic and transcriptomic findings provide significant insight into the molecular changes that occur in hBMECs during T. gondii infection.

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Section: Discussionsupporting

confidence: 88%

Illuminating Host-Parasite Interaction at the Cellular and Subcellular Levels with Infrared Microspectroscopy

Elsheikha

Al-sandaqchi

Harun

et al. 2022

Cells

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“…We identified differentially expressed host genes for seven out of ten effector proteins that have been validated in the highly virulent type I T. gondii RH strain used in this experiment: MYR1 14 , HCE1/TEEGR 15,16 , IST 17,18 , GRA16 19 , GRA24 20 , GRA28 21,22 , and ROP16 23 (Figure 1L, Supplementary Data 2). We did not find any significantly differentially expressed genes for the effectors GRA6 24 , GRA7 25 or ROP18 26 . These were among the genes for which we recovered the fewest single cell transcriptomes and so have less statistical power; however, there is also less evidence that these effectors induce changes in the host cell transcriptome during a physiological infection.…”

Section: Optimisation Of a Direct-capture Perturb-seq Vector For Toxo...contrasting

confidence: 57%

Mapping host-microbe transcriptional interactions by dual perturb-seq

Butterworth

Kordova

Chandrasekaran

et al. 2023

Preprint

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Intracellular pathogens and other endosymbionts reprogram host cell transcription to suppress immune responses and recalibrate biosynthetic pathways. This reprogramming is critical in determining the outcome of infection or colonisation. Here, we combine pooled CRISPR knockout screening with dual host–microbe single–cell RNA–sequencing to identify the molecular mediators of these transcriptional interactions, a method we term dual perturb–seq. Applying dual perturb–seq to the intracellular pathogenToxoplasma gondii, we are able to identify previously uncharacterised effector proteins and directly infer their function from the transcriptomic data. We show thatTgGRA59 contributes to the export of other effector proteins from the parasite into the host cell and identify a novel effector,TgSOS1, that is necessary for sustained host STAT6 signalling and thereby contributes to parasite immune evasion and persistence. Together, this work demonstrates a novel tool that can be broadly adapted to interrogate host–microbe transcriptional interactions and reveal mechanisms of infection and immune evasion.

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“…The ASEs of A549 cells caused by ML-ESPs are still a mystery. A few studies have examined the ASEs in cells that had been exposed to parasites, such as Toxoplasma gondii rhoptry protein 18 ( 38 ), rhoptry organelle protein 17 ( 39 ) and Trypanosoma cruzi ( 40 ). By contrasting five splicing products, including SE, A5SS, A3SS, MXE, and RI, we looked into the function of ML-ESPs in the regulation of A549 cellular ASEs.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome profiling of A549 non-small cell lung cancer cells in response to Trichinella spiralis muscle larvae excretory/secretory products

Wang,

Zhu,

et al. 2023

Front. Vet. Sci.

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Trichinella spiralis (T. spiralis) muscle-larva excretory/secretory products (ML-ESPs) is a complex array of proteins with antitumor activity. We previously demonstrated that ML-ESPs inhibit the proliferation of A549 non-small cell lung cancer (NSCLC) cell line. However, the mechanism of ML-ESPs against A549 cells, especially on the transcriptional level, remains unknow. In this study, we systematically investigated a global profile bioinformatics analysis of transcriptional response of A549 cells treated with ML-ESPs. And then, we further explored the transcriptional regulation of genes related to glucose metabolism in A549 cells by ML-ESPs. The results showed that ML-ESPs altered the expression of 2,860 genes (1,634 upregulated and 1,226 downregulated). GO and KEGG analysis demonstrated that differentially expressed genes (DEGs) were mainly associated with pathway in cancer and metabolic process. The downregulated genes interaction network of metabolic process is mainly associated with glucose metabolism. Furthermore, the expression of phosphofructokinase muscle (PFKM), phosphofructokinase liver (PFKL), enolase 2 (ENO2), lactate dehydrogenase B (LDHB), 6-phosphogluconolactonase (6PGL), ribulose-phosphate-3-epimerase (PRE), transketolase (TKT), transaldolase 1 (TALDO1), which genes mainly regulate glycolysis and pentose phosphate pathway (PPP), were suppressed by ML-ESPs. Interestingly, tricarboxylic acid cycle (TCA)-related genes, such as pyruvate dehydrogenase phosphatase 1 (PDP1), PDP2, aconitate hydratase 1 (ACO1) and oxoglutarate dehydrogenase (OGDH) were upregulated by ML-ESPs. In summary, the transcriptome profiling of A549 cells were significantly altered by ML-ESPs. And we also provide new insight into how ML-ESPs induced a transcriptional reprogramming of glucose metabolism-related genes in A549 cells.

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ROP18-Mediated Transcriptional Reprogramming of HEK293T Cell Reveals New Roles of ROP18 in the Interplay Between Toxoplasma gondii and the Host Cell

Cited by 8 publications

References 86 publications

Illuminating Host-Parasite Interaction at the Cellular and Subcellular Levels with Infrared Microspectroscopy

Illuminating Host-Parasite Interaction at the Cellular and Subcellular Levels with Infrared Microspectroscopy

Mapping host-microbe transcriptional interactions by dual perturb-seq

Transcriptome profiling of A549 non-small cell lung cancer cells in response to Trichinella spiralis muscle larvae excretory/secretory products

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