RNA seq analysis from the kidney of pycard mutant adult zebrafish in Mycobacterium marinum infection
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ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE189627 | GEO | 2024/07/04
REPOSITORIES: GEO
Similar Datasets
Project description:Inflammasome regulates the host response to intracellular pathogens including mycobacteria. We have previously shown that the course of M. marinum infection in adult zebrafish (Danio rerio) has similar features than the course of tuberculosis in human. Here we have investigated the role of the inflammasome adaptor pycard in M. marinum infection in zebrafish with two CRISPR/Cas9 mutagenesis generated zebrafish line. Adult zebrafish devoid of pycard showed impaired survival and increased bacterial burden in M. marinum infection. Transcriptome analysis with RNA sequencing of a kidney derived neutrophils of M. marinum infected fish homozygous for pycardptu4 mutation revealed differentially expressed genes compared to WT controls. Differentially expressed genes were associated with neutrophil degranulation, haematopoiesis and PI3K signalling are differentially expressed in the pycard deficient neutrophils when compared to wild type controls.
2024-07-03 | GSE270136 | GEO
Project description:Transcriptome profiling of adult zebrafish at the late stage of chronic tuberculosis due to Mycobacterium marinum infection.
2005-08-17 | E-MEXP-405 | biostudies-arrayexpress
Project description:Mycobacterium marinum infection in zebrafish (Danio rerio) has been widely used to study human tuberculosis because the bacteria causing these two diseases are close relatives. We studied the zebrafish immune response to M. marinum infection through a whole-genome level transcriptome analysis. In addition, we carried out a medium-scale forward genetic screen to identify genes underlying defense mechanisms against M. marinum infection in zebrafish. Our aim was to gain more information about the genetic mechanisms important in the immune defense against human tuberculosis. In this screen, we identified a mutant zebrafish line with impaired resistance to a low-dose M. marinum infection. In this line, the transcriptome analysis at 14 days post infection revealed decreased expression of a gene homologous to human UNC119 which has been shown to have a role in T cell activation.
2019-10-16 | GSE118350 | GEO
Project description:Zebrafish Mycobacterium marinum infection has been widely used to model human tuberculosis because these two diseases share common features, e.g. latency, granuloma formation and reactivation. Here we infected adult zebrafish with a low dose of M. marinum, which usually leads to a chronic infection. At 14 days post infection we performed microarray analysis to characterize the immune response against this infection. Analysis was done using total RNA extracted from the abdominal organs of zebrafish. Our aim was to find novel genes underlying host defense mechanisms against M. marinum infection in zebrafish, and thus to produce novel information that is valuable when developing new treatments for human tuberculosis.
2019-02-01 | GSE120552 | GEO
Project description:Proteins expressed and exported out of the mycobacterial biofilm cells into granulomatous environment during infection were identified by LC-MS/MS. To this end, adult 5- to 10-month-old female AB wild-type zebrafish (Danio rerio) were infected with 4-day old M. marinum ATCC927 (carrying the pTEC27 plasmid expressing the tdTomato fluorescent protein) cells. After 8 weeks post infection, ten zebrafish were euthanized, and red fluorescent mycobacterial granulomas were carefully dissected from the zebrafish ovaries. Ten granulomas were collected per tube, frozen on dry ice and stored at -80 °C until preparation for proteomics. Altogether, ten replicate samples, each with ten mycobacterial granulomas, were subjected to protein extraction and LC-MS/MS identification.
2023-03-06 | PXD039416 | Pride
Project description:MyD88 is an adaptor protein in Toll-like receptor and interleukin 1 receptor mediated signaling pathways that plays an essential role in activation of immune responses following pathogen recognition. We investigate that role in the zebrafish embryo model by using a zebrafish mutant line that contains a premature stop condon in the gene encoding MyD88, leading to a truncated protein that lacks domains important for its normal function. We infected these MyD88 mutants and wildtype individuals with Mycobacterium marinum to compare the resulting immune response by transcriptome profiling on total RNA isolated from single embryos. Autophagy regulator dram1 was identified as one of the MyD88-dependent genes. This RNAseq analysis was used to determine the effect of a truncation of the MyD88 protein on the innate immune response of zebrafish embryos during infection with Mycobacterium marinum. Myd88 mutant and wild type embryos were derived by incrossing homozygous myd88 mutant parents (allele hu3568, van der Vaart et al., 2013, Disease models & mechanisms 6, 841-854) or their wildtype siblings. RNA was isolated from pools of 20 embryos at 4 days post infection (4 dpi). The following treatment groups were used: homozygous mutants mock-injected with PBS/2%PVP 4 dpi, (2) wildtype siblings mock-injected with PBS/2%PVP 4dpi, (3) M. marinum-infected homozygous mutants 4dpi, (4) M. marinum-infected wildtype siblings 4dpi. Embryos were grown at 28.5M-bM-^@M-^S30M-BM-0C in egg water and manually dechorionated at 24 hours post fertilization (hpf). Subsequently, embryos were infected at 28 hpf by micro-injecting 200 colony forming units (CFU) of Mycobacterium marinum Mma20 bacteria into the caudal vein, or were mock-injected with buffer (PBS/2%PVP) as a control. After injections embryos were transferred into fresh egg water and incubated for 4 days at 28M-BM-0C. After the incubation period, single embryos were snap-frozen in liquid nitrogen and RNA was isolated for RNAseq analysis.
2014-06-01 | E-GEOD-49186 | biostudies-arrayexpress
Project description:Granulomas are the pathological hallmark of tuberculosis (TB). In individuals latently infected with Mycobacterium tuberculosis (M. tb), the bacteria are thought to reside within the granulomas in a nonreplicating dormant state due to the lack of oxygen and nutrients. However, a portion of these individuals will develop active TB and little is known on the bacterial mechanisms/factors involved in this process. In this study, we found that WhiB4, an oxygen sensor and a transcription factor, plays a critical role in disease progression and reactivation of Mycobacterium marinum (M. marinum) infection in zebrafish. We show that the whiB4 mutant of M. marinum caused latent infection in adult zebrafish, which is characterized by the stable bacterial loads, constant number of non-necrotized granulomas in fewer organs, and reduced immune responses compared to zebrafish infected with the wild type bacteria or the complemented strain. The mutant bacteria in zebrafish were also less responsive to antibiotic treatments. Moreover, the whiB4 mutant was defective in resuscitation from hypoxia-induced dormancy and that the DosR regulon was dysregulated in the mutant. Taken together, our results suggest that WhiB4 is a major driver of reactivation from latent infection and that WhiB4 is an attractive target for the development of novel therapeutics, which may help to prevent the reactivation of latent infection thereby reducing the incidences of active TB.
2021-11-22 | GSE189123 | GEO
Project description:Granulomas are the pathological hallmark of tuberculosis (TB). In individuals latently infected with Mycobacterium tuberculosis (M. tb), the bacteria are thought to reside within the granulomas in a nonreplicating dormant state due to the lack of oxygen and nutrients. However, a portion of these individuals will develop active TB and little is known on the bacterial mechanisms/factors involved in this process. In this study, we found that WhiB4, an oxygen sensor and a transcription factor, plays a critical role in disease progression and reactivation of Mycobacterium marinum (M. marinum) infection in zebrafish. We show that the whiB4 mutant of M. marinum caused latent infection in adult zebrafish, which is characterized by the stable bacterial loads, constant number of non-necrotized granulomas in fewer organs, and reduced immune responses compared to zebrafish infected with the wild type bacteria or the complemented strain. The mutant bacteria in zebrafish were also less responsive to antibiotic treatments. Moreover, the whiB4 mutant was defective in resuscitation from hypoxia-induced dormancy and that the DosR regulon was dysregulated in the mutant. Taken together, our results suggest that WhiB4 is a major driver of reactivation from latent infection and that WhiB4 is an attractive target for the development of novel therapeutics, which may help to prevent the reactivation of latent infection thereby reducing the incidences of active TB.
2021-06-16 | GSE178190 | GEO
Project description:Granulomas are the pathological hallmark of tuberculosis (TB). In individuals latently infected with Mycobacterium tuberculosis (M. tb), the bacteria are thought to reside within the granulomas in a nonreplicating dormant state due to the lack of oxygen and nutrients. However, a portion of these individuals will develop active TB and little is known on the bacterial mechanisms/factors involved in this process. In this study, we found that WhiB4, an oxygen sensor and a transcription factor, plays a critical role in disease progression and reactivation of Mycobacterium marinum (M. marinum) infection in zebrafish. We show that the whiB4 mutant of M. marinum caused latent infection in adult zebrafish, which is characterized by the stable bacterial loads, constant number of non-necrotized granulomas in fewer organs, and reduced immune responses compared to zebrafish infected with the wild type bacteria or the complemented strain. The mutant bacteria in zebrafish were also less responsive to antibiotic treatments. Moreover, the whiB4 mutant was defective in resuscitation from hypoxia-induced dormancy and that the DosR regulon was dysregulated in the mutant. Taken together, our results suggest that WhiB4 is a major driver of reactivation from latent infection and that WhiB4 is an attractive target for the development of novel therapeutics, which may help to prevent the reactivation of latent infection thereby reducing the incidences of active TB.
2021-06-16 | GSE178186 | GEO
Project description:Granulomas are the pathological hallmark of tuberculosis (TB). In individuals latently infected with Mycobacterium tuberculosis (M. tb), the bacteria are thought to reside within the granulomas in a nonreplicating dormant state due to the lack of oxygen and nutrients. However, a portion of these individuals will develop active TB and little is known on the bacterial mechanisms/factors involved in this process. In this study, we found that WhiB4, an oxygen sensor and a transcription factor, plays a critical role in disease progression and reactivation of Mycobacterium marinum (M. marinum) infection in zebrafish. We show that the whiB4 mutant of M. marinum caused latent infection in adult zebrafish, which is characterized by the stable bacterial loads, constant number of non-necrotized granulomas in fewer organs, and reduced immune responses compared to zebrafish infected with the wild type bacteria or the complemented strain. The mutant bacteria in zebrafish were also less responsive to antibiotic treatments. Moreover, the whiB4 mutant was defective in resuscitation from hypoxia-induced dormancy and that the DosR regulon was dysregulated in the mutant. Taken together, our results suggest that WhiB4 is a major driver of reactivation from latent infection and that WhiB4 is an attractive target for the development of novel therapeutics, which may help to prevent the reactivation of latent infection thereby reducing the incidences of active TB.
2021-06-16 | GSE178188 | GEO