Hydrogen sulfide dysregulates the immune response by suppressing central carbon metabolism to promote tuberculosis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA601120 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10895326_1.fastq.gz | Fastqsanger.gz | |||
| SRR10895326_2.fastq.gz | Fastqsanger.gz | |||
| SRR10895327_1.fastq.gz | Fastqsanger.gz | |||
| SRR10895327_2.fastq.gz | Fastqsanger.gz | |||
| SRR10895328_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:The ubiquitous gasotransmitter hydrogen sulfide (H2S) has been recognised to play a crucial role in human health. However, a role for host H2S in pathogenesis has not yet been demonstrated. Using cystathionine -lyase (CSE) deficient mice, we demonstrated an unexpected role of H2S in Mtb pathogenesis. We showed that Mtb-infected CSE-/- mice survive longer than wild-type mice, and support reduced pathology and lower bacterial burdens in the lung, spleen and liver. Similarly, in vitro Mtb infection of macrophages resulted in reduced colony forming units (CFUs) in CSE-/-cells. Chemical complementation of infected wild-type and CSE-/-macrophages using the slow H2S releaser GYY3147 and the CSE inhibitor DL-propargylglycine demonstrated that H2S is the effector molecule regulating Mtb survival in macrophages. Furthermore, we demonstrate that CSE promotes an excessive innate immune response, suppresses the adaptive immune response and reduces circulating IL1β, IL-6, TNFα, and IFN-γ levels in response to Mtb infection. Notably, Mtb infected CSE-/- macrophages show increased flux through glycolysis and the pentose phosphate pathway thereby establishing a critical link between H2S and central metabolism. Our data suggest that excessive H2S produced by the infected wild type mice reduce HIF-1α levels, thereby suppressing glycolysis and production of IL-1β, IL-6 and IL-12, and increasing bacterial burden. Clinical relevance was demonstrated by the spatial distribution of H2S producing enzymes in human necrotic, non-necrotic and cavitary pulmonary TB lesions. In summary, CSE exacerbates TB pathogenesis by altering immunometabolism in mice and inhibiting CSE or modulating glycolysis are potential targets for host-directed TB control.
2020-04-06 | GSE143619 | GEO
Project description:The ubiquitous gasotransmitter hydrogen sulfide (H2S) has been recognized to play a crucial role in human health. Using cystathionine γ-lyase (CSE)-deficient mice, we demonstrate an unexpected role of H2S in Mycobacterium tuberculosis (Mtb) pathogenesis. We showed that Mtb-infected CSE-/- mice survive longer than WT mice, and support reduced pathology and lower bacterial burdens in the lung, spleen, and liver. Similarly, in vitro Mtb infection of macrophages resulted in reduced colony forming units in CSE-/- cells. Chemical complementation of infected WT and CSE-/- macrophages using the slow H2S releaser GYY3147 and the CSE inhibitor DL-propargylglycine demonstrated that H2S is the effector molecule regulating Mtb survival in macrophages. Furthermore, we demonstrate that CSE promotes an excessive innate immune response, suppresses the adaptive immune response, and reduces circulating IL-1β, IL-6, TNF-α, and IFN-γ levels in response to Mtb infection. Notably, Mtb infected CSE-/- macrophages show increased flux through glycolysis and the pentose phosphate pathway, thereby establishing a critical link between H2S and central metabolism. Our data suggest that excessive H2S produced by the infected WT mice reduce HIF-1α levels, thereby suppressing glycolysis and production of IL-1β, IL-6, and IL-12, and increasing bacterial burden. Clinical relevance was demonstrated by the spatial distribution of H2S-producing enzymes in human necrotic, nonnecrotic, and cavitary pulmonary tuberculosis (TB) lesions. In summary, CSE exacerbates TB pathogenesis by altering immunometabolism in mice and inhibiting CSE or modulating glycolysis are potential targets for host-directed TB control.
| S-EPMC7104411 | biostudies-literature
Project description:Interventions: Case series:nill;The control group:nill
Primary outcome(s): Hydrogen sulfide;Pathological diagnosis
Study Design: Case-Control study
| 2671665 | ecrin-mdr-crc
Project description:Stress response of Methylococcus capsulatus str.Bath toward hydrogen sulfide (H2S) was investigated via physiological study and transcriptomic profiling. M. capsulatus (Bath) can grow and tolerate up to 0.75%vol H2S in headspace. Vast change in pH suggests biological relevant sulfide oxidation. Dozens of H2S-sensitive genes were identified from comparison of cell transcriptome in different H2S concentrations. Mc sulfide quinone reductase (SQR) and persulfide dioxygenase were found to be active during sulfide detoxification. Moreover, xoxF, a novel lanthanide(Ln)-dependent methanol dehydrogenase (MDH) was overexpressed in H2S while mxaF, a calcium-dependent MDH, was down-regulated, and such MDH switch phenomenon is also well known to be induced by addition of lanthanide via an as-yet-unknown mechanism. Activities in quorum sensing and RND efflux pump also suggest their role in sulfide detoxification, and might provide insight on the xoxF/mxaF switch mechanism.
2021-12-24 | GSE192351 | GEO
Project description:The aim of this experiment was to determine how exposure of Hydrogen sulfide impacts gene expression in Mycobacterium tuberculosis. RNA was isolated from actively growing mycobacterial cells (0.6-0.8 OD600) using Trizol according to established protocols (27). Briefly, cells were exposed to 25 µM GYY4137 for 1 hr under carefully controlled conditions (n=3/group) and RNA isolated. Unexposed cells received spent GYY4137 (without any capacity to produce Hydrogen sulfide).
2020-01-04 | E-MTAB-7421 | biostudies-arrayexpress
Project description:Hydrogen sulfide (H2S) as an important gasotransmitter has fundamental roles in human diseases. The cellular effect of H2S has received lots of attention recently. H2S can affect ion channels, transcription factors and kinase in mammals. The mechanism of cellular effect of H2S is not completely understood. We used fission yeast as a model organism to study the global transcriptional profile in response to H2S by microarray.
2012-06-15 | GSE30025 | GEO
Project description:Hydrogen sulfide (H2S) is formed naturally from L-cysteine in a variety of mammalian and non-mammalian cells. To date, numerous biological effects have been ascribed to H2S including control of cardiovascular, immune and nervous function. Over or under production of H2S has been observed in several disease states including hypertension and inflammation. In addition, it has been stipulated that H2S may affect the ageing process. The model nematode Caenorhabditis elegans is ideally suited for assessing drug effects on lifespan since it is relatively short-lived, can be easily exposed to drugs and its genome is fully sequenced and widely annotated.
2013-07-30 | GSE16975 | GEO
Project description:As one of the most important environmental factors, heat stress (HS) has been found to affect various biological activities of organisms such as growth, signal transmission, primary metabolism and secondary metabolism. Ganoderma lucidum has become a potential model system for evaluating how environmental factors regulate the secondary metabolism of basidiomycetes. Previous research showed that HS can induce the biosynthesis of ganoderic acids (GAs). In this study, we found the existence of hydrogen sulfide in Ganoderma lucidum; moreover, HS increased GAs biosynthesis and could affect the hydrogen sulfide content. We found that sodium hydrosulfide (NaHS), an exogenous donor of hydrogen sulfide, could revert the increased GAs biosynthesis elicited by HS. This result indicated that an increased content of hydrogen sulfide, within limits, was associated with HS-induced GAs biosynthesis. Our results further showed that the GAs content was increased in CBS-silenced strains and could be reverted to WT strain levels by the addition of NaHS. Transcriptomic analyses indicated that that H2S can affect various intracellular signal pathways and physiological processes in G. lucidum. Further studies showed that H2S could affect the intracellular calcium concentration and thus regulate the biosynthesis of GAs. This study demonstrated that hydrogen sulfide is involved in the regulation of secondary metabolic processes induced by heat stress in filamentous fungi.
2021-10-12 | GSE121270 | GEO
Project description:Hydrogen sulfide (H2S) is formed naturally from L-cysteine in a variety of mammalian and non-mammalian cells. To date, numerous biological effects have been ascribed to H2S including control of cardiovascular, immune and nervous function. Over or under production of H2S has been observed in several disease states including hypertension and inflammation. In addition, it has been stipulated that H2S may affect the ageing process. The model nematode Caenorhabditis elegans is ideally suited for assessing drug effects on lifespan since it is relatively short-lived, can be easily exposed to drugs and its genome is fully sequenced and widely annotated. The global transcriptome of control nematodes (raised using standardized laboratory conditions) was compared to nematodes exposed to 100 uM GYY4137 (morpholin-4-ium 4 methoxyphenyl(morpholino) phosphinodithioate), a slow releasing H2S donor drug.
2013-07-30 | E-GEOD-16975 | biostudies-arrayexpress
Project description:Hydrogen sulfide (H2S), present in abundance in the mammalian brain, has recently been demonstrated to induce a dose- and time-dependent apoptotic-necrotic continuum in murine primary cortical neurons, which was successfully attenuated upon application of N-methyl-D-aspartate (NMDA) receptor antagonist. The current study focused on gaining an insight into the molecular mechanisms of H2S–mediated neuronal death pertaining to NMDA receptors activation through global gene expression comparisons.
2013-01-23 | GSE16035 | GEO