Trancriptional Profile of Mycobacterium tuberculosis Replicating at in Artificial Intraocular Fluid
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PROVIDER: PRJNA894495 | ENA |
REPOSITORIES: ENA
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Project description:Intraocular tuberculosis (IOTB) is a significant cause of visual morbidity in TB-endemic countries. However, pathogenesis of Mycobacterium tuberculosis (M. tb) in the ocular compartment is poorly defined. IOTB is paucibacillary in a vast majority of patients although M. tb has been detected in both the retinal pigment epithelial (RPE) cells (Rao et al. 2006) and in the intraocular fluid (IOF) (Aggarwal et al., 2016; Bajgai et al., 2017) in some cases. In this study, we have examined the replication and whole genome transcriptome of M. tb in an IOF model (artificial IOF; AIOF) (Macri et al., 2015). Results show that, as reported for transcriptional profiles of M. tb in sputum (Sharma et al., 2017) and in a starvation model (PBS) (Betts et al., 2002), genes involved in active replication and aerobic respiration are either downregulated or not differentially expressed in the AIOF. In ARPE-19 cells (human RPE cell line), M. tb replicates poorly and exhibits a quiescent phenotype (Abhishek et al., 2018). As in sputum, PBS, and ARPE-19 cells, M. tb in AIOF downregulates genes of the DosR regulon indicating the suppression of dormancy. Importantly, genes encoding ESAT-6 and ESAT-6-like proteins are also downregulated or not differentially expressed in sputum, AIOF and ARPE-19 cells. This is stark contrast to the transcriptome of M. tb in alveolar epithelial cells (Ryndak et al., 2015) and in blood (Ryndak et al. 2014). These results paint a scenario wherein M. tb acquires a replicative and invasive phenotype when it infects a new host and disseminates systemically. However, M. tb acquires a quiescent phenotype upon reaching its final niche in an extrapulmonary site, the ocular environment.
2022-11-30 | GSE216603 | GEO
Project description:Vibrio parahaemolyticus is the causative agent of food-borne gastroenteritis disease. Once consumed, human acid gastric fluid is perhaps one of the most important environmental stresses imposed on the bacterium. Herein, for the first time, we investigated Vibrio parahaemolyticus CHN25 response to artificial gastric fluid (AGF) stress by transcriptomic analysis. The bacterium at logarithmic growth phase (LGP) displayed lower survival rates than that at stationary growth phase (SGP) under a sub-lethal acid condition (pH 4.9). Transcriptome data revealed that 11.6% of the expressed genes in Vibrio parahaemolyticus CHN25 was up-regulated in LGP cells after exposed to AGF (pH 4.9) for 30 min, including those involved in sugar transport, nitrogen metabolism, energy production and protein biosynthesis, whereas 14.0% of the genes was down-regulated, such as ABC transporter and flagellar biosynthesis genes. In contrast, the AGF stress only elicited 3.4% of the genes from SGP cells, the majority of which were attenuated in expression. Moreover, the number of expressed regulator genes was also substantially reduced in SGP cells. Comparison of transcriptome profiles further revealed forty-one growth-phase independent genes in the AGF stress, however, half of which displayed distinct expression features between the two growth phases. Vibrio parahaemolyticus seemed to have evolved a number of molecular strategies for coping with the acid stress. The data here will facilitate future studies for environmental stresses and pathogenicity of the leading food-borne pathogen worldwide. When V.parahemolyticus CHN25 grown to log phase and stationary phase at 37°C in TSB-3% NaCl, different cultures were subsequently exposed to artificial gastric fluid at 37°C for 30 min. Two independent experiments were performed at each phase for microarray expreriments.
2015-06-30 | E-GEOD-63167 | biostudies-arrayexpress
Project description:The goal of this study was to determine the effect of dexamethasone treatment on trancriptional sigantures and pathways of sarcoidosis monocytes.
2020-05-20 | GSE150049 | GEO
Project description:Vibrio parahaemolyticus is the causative agent of food-borne gastroenteritis disease. Once consumed, human acid gastric fluid is perhaps one of the most important environmental stresses imposed on the bacterium. Herein, for the first time, we investigated Vibrio parahaemolyticus CHN25 response to artificial gastric fluid (AGF) stress by transcriptomic analysis. The bacterium at logarithmic growth phase (LGP) displayed lower survival rates than that at stationary growth phase (SGP) under a sub-lethal acid condition (pH 4.9). Transcriptome data revealed that 11.6% of the expressed genes in Vibrio parahaemolyticus CHN25 was up-regulated in LGP cells after exposed to AGF (pH 4.9) for 30 min, including those involved in sugar transport, nitrogen metabolism, energy production and protein biosynthesis, whereas 14.0% of the genes was down-regulated, such as ABC transporter and flagellar biosynthesis genes. In contrast, the AGF stress only elicited 3.4% of the genes from SGP cells, the majority of which were attenuated in expression. Moreover, the number of expressed regulator genes was also substantially reduced in SGP cells. Comparison of transcriptome profiles further revealed forty-one growth-phase independent genes in the AGF stress, however, half of which displayed distinct expression features between the two growth phases. Vibrio parahaemolyticus seemed to have evolved a number of molecular strategies for coping with the acid stress. The data here will facilitate future studies for environmental stresses and pathogenicity of the leading food-borne pathogen worldwide.
2015-06-30 | GSE63167 | GEO
Project description:Previous studies indicated that activation of glial cells and inflammatory responses are triggering factors of glaucomatous optic neuropathy. In particular, neurotoxic reactive astrocytes have been found to play a significant role in retinal ganglion cell damage. Furthermore, research showed that activation of glial cells is not dependent on retinal ganglion cell injury, but rather a direct response to pathological elevation of intraocular pressure. However, the molecular mechanism by which elevated intraocular pressure triggers glial activation through mechanical forces remains unknown. By spatial transcriptome sequencing, our study revealed that the neurotoxic astrocyte would rapidly be reactivated in the optic nerve head under elevated intraocular pressure in vivo.
2024-08-31 | GSE241192 | GEO
Project description:The goal of this study was to determine the effect of dexamethasone treatment on trancriptional signatures and pathways of sarcoidosis AMs.
2020-05-20 | GSE150842 | GEO
Project description:Ocular immune privilege (IP) limits immune surveillance of intraocular tumors as certain immunogenic tumor cell lines (P815, E.G7-OVA) that are rejected when transplanted in the skin grow progressively when placed in the anterior chamber (a.c.) of the eye. As splenectomy (SPLNX) is known to terminate ocular IP, we characterized immune mechanisms responsible for spontaneous rejection of intraocular tumors in SPLNX mice as a first step toward identifying how to restore tumoricidal activity within the eye. Microarray data showed a 3-fold increase in interferon (IFN)-γ and a 2.7-fold increase in Fas ligand (FasL). There was a robust increase in transcripts (127 of 408 surveyed) from interferon (IFN)-stimulated genes and a marked decrease (in 40 of 192 surveyed) in the expression of cell-cycle-associated genes. Non-microarray data confirmed that IFNγ, FasL and CD8+ T cells but not perforin or TNFα were required for elimination of intraocular E.G7-OVA tumors that culminated in destruction of the eye (ocular phthsis). IFNγ and FasL did not target tumor cells directly as the majority of SPLNX IFNγR1-/- mice and Fas-defective lpr mice failed to eliminate ocular E.G7-OVA tumors that expressed Fas and IFNγR1. Bone marrow chimeras showed that immune cell expression of IFNγR1 and Fas was critical and that SPLNX increased the frequency of activated macrophages within ocular tumors in an IFNγ- and Fas/FasL-dependent manner. Rejection of intraocular tumors was associated with increased ocular mRNA expression of several inflammatory genes including FasL, NOS2, CXCL2 and T-bet. Our data support a model in which IFNγ- and Fas/FasL-dependent activation of intratumoral macrophage by CD8+ T cells promotes severe intraocular inflammation that indirectly eliminates intraocular tumors by inducing phthisis. The immunosuppressive mechanisms which maintain ocular IP likely interfere with the interaction between CD8+ T cells and macrophage to limit immunosurveillance of intraocular tumors. C57BL/6 mice that were splenectomized (Tumor_splnx) or were not surgically manipulated (Tumor_intact) were challenged with 10^4 luciferase-expressing E.G7-OVA cells injected into the anterior chamber of the eye. Fifteen days later, the animals were euthanized and tumor-bearing eyes were removed.
2014-07-01 | E-GEOD-57101 | biostudies-arrayexpress
Project description:Reactive astrocytes are typically studied in models that cause irreversible mechanical damage to axons, neuronal cell bodies, and glia. We evaluated the response of astrocytes in the optic nerve head to a subtle injury induced by a brief, mild elevation of the intraocular pressure. Astrocytes demonstrated reactive remodeling showing hypertrophy, process retraction and simplification of their shape. We used microarray to indentify differentially expressed genes and to investigate the molecular mechanisms of astrogliosis in response to this subtle injury. Six- to eight-week old C57Bl/6 male mice were used in this experiment. One eye underwent an elevation in intraocular pressure to 30 mmHg for 1 hour and then allowed to recover for 3 days. The contralateral eye served as a control. Due to the small tissue size of the mouse optic nerve head, two optic nerve heads were pooled together for each microarray chip. We used 10 mice to generate five biological replicates for each condition.
2013-05-17 | E-GEOD-40009 | biostudies-arrayexpress
Project description:Ocular immune privilege (IP) limits immune surveillance of intraocular tumors as certain immunogenic tumor cell lines (P815, E.G7-OVA) that are rejected when transplanted in the skin grow progressively when placed in the anterior chamber (a.c.) of the eye. As splenectomy (SPLNX) is known to terminate ocular IP, we characterized immune mechanisms responsible for spontaneous rejection of intraocular tumors in SPLNX mice as a first step toward identifying how to restore tumoricidal activity within the eye. Microarray data showed a 3-fold increase in interferon (IFN)-γ and a 2.7-fold increase in Fas ligand (FasL). There was a robust increase in transcripts (127 of 408 surveyed) from interferon (IFN)-stimulated genes and a marked decrease (in 40 of 192 surveyed) in the expression of cell-cycle-associated genes. Non-microarray data confirmed that IFNγ, FasL and CD8+ T cells but not perforin or TNFα were required for elimination of intraocular E.G7-OVA tumors that culminated in destruction of the eye (ocular phthsis). IFNγ and FasL did not target tumor cells directly as the majority of SPLNX IFNγR1-/- mice and Fas-defective lpr mice failed to eliminate ocular E.G7-OVA tumors that expressed Fas and IFNγR1. Bone marrow chimeras showed that immune cell expression of IFNγR1 and Fas was critical and that SPLNX increased the frequency of activated macrophages within ocular tumors in an IFNγ- and Fas/FasL-dependent manner. Rejection of intraocular tumors was associated with increased ocular mRNA expression of several inflammatory genes including FasL, NOS2, CXCL2 and T-bet. Our data support a model in which IFNγ- and Fas/FasL-dependent activation of intratumoral macrophage by CD8+ T cells promotes severe intraocular inflammation that indirectly eliminates intraocular tumors by inducing phthisis. The immunosuppressive mechanisms which maintain ocular IP likely interfere with the interaction between CD8+ T cells and macrophage to limit immunosurveillance of intraocular tumors.
2014-07-01 | GSE57101 | GEO