Th17 cell plasticity towards a T-bet-dependent Th1 phenotype is required for bacterial control in Staphylococcus aureus infection
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE199857 | GEO | 2022/04/05
REPOSITORIES: GEO
Similar Datasets
Project description:Th17 cell plasticity towards a T-bet-dependent Th1 phenotype is required for bacterial control in Staphylococcus aureus infection
| PRJNA821838 | ENA
Project description:Staphylococcus aureus pneumonia causes significant morbidity and mortality. Alpha-hemolysin (Hla), a pore-forming cytotoxin of S. aureus, has been identified through animal models of pneumonia as a critical virulence factor that induces lung injury. In spite of considerable molecular knowledge of how this cytotoxin injures the host, the precise host response to Hla in the context of infection remains poorly understood. We employed whole-genome expression profiling of infected lung to define the host response to wild-type S. aureus compared with an Hla-deficient isogenic mutant in experimental pneumonia. These data provide a complete expression profile at four and at twenty-four hours post-infection, revealing a unique response to the toxin-expressing strain. Gene ontogeny analysis revealed significant differences in the extracellular matrix and cardiomyopathy pathways, both of which govern cellular interactions in the tissue microenvironment. Evaluation of individual transcript responses to Hla-secreting bacteria was notable for upregulation of host cytokine and chemokine genes, including the p19 subunit of interleukin-23. Consistent with this observation, the cellular immune response to infection was characterized by a prominent TH17 response to wild-type staphylococci. These findings define specific host mRNA responses to Hla-producing S. aureus, coupling the pulmonary TH17 response to the presence of this cytotoxin. Expression profiling to define the host response to a single virulence factor proved to be a valuable tool in identifying pathways for further investigation in S. aureus pneumonia. This approach may be broadly applicable to the study of bacterial toxins, defining host pathways that can be targeted to mitigate toxin-induced disease. Animals were treated with PBS, S. aureus wild-type, or S. aureus Hla-deficient isogenic mutant.
2012-05-20 | E-GEOD-38053 | biostudies-arrayexpress
Project description:Staphylococcus aureus pneumonia causes significant morbidity and mortality. Alpha-hemolysin (Hla), a pore-forming cytotoxin of S. aureus, has been identified through animal models of pneumonia as a critical virulence factor that induces lung injury. In spite of considerable molecular knowledge of how this cytotoxin injures the host, the precise host response to Hla in the context of infection remains poorly understood. We employed whole-genome expression profiling of infected lung to define the host response to wild-type S. aureus compared with an Hla-deficient isogenic mutant in experimental pneumonia. These data provide a complete expression profile at four and at twenty-four hours post-infection, revealing a unique response to the toxin-expressing strain. Gene ontogeny analysis revealed significant differences in the extracellular matrix and cardiomyopathy pathways, both of which govern cellular interactions in the tissue microenvironment. Evaluation of individual transcript responses to Hla-secreting bacteria was notable for upregulation of host cytokine and chemokine genes, including the p19 subunit of interleukin-23. Consistent with this observation, the cellular immune response to infection was characterized by a prominent TH17 response to wild-type staphylococci. These findings define specific host mRNA responses to Hla-producing S. aureus, coupling the pulmonary TH17 response to the presence of this cytotoxin. Expression profiling to define the host response to a single virulence factor proved to be a valuable tool in identifying pathways for further investigation in S. aureus pneumonia. This approach may be broadly applicable to the study of bacterial toxins, defining host pathways that can be targeted to mitigate toxin-induced disease.
2012-05-21 | GSE38053 | GEO
Project description:The transcription level of a rex-deficient S. aureus mutant in comparison to its parental strain S. aureus SH1000 was analyzed using DNA microarrays.
2009-12-31 | GSE17128 | GEO
Project description:IL-17-producing T helper (TH17) cells have been selected through evolution for their ability to control fungal and bacterial infections. It is also firmly established that their aberrant generation and activation results in autoimmune conditions. Using a characterized potent and selective small molecule inhibitor, we show that the bromodomain and extra-terminal domain (BET) family of chromatin adaptors plays fundamental and selective roles in human and murine TH17 differentiation from naM-CM-/ve CD4+ T cells, as well as in the activation of previously differentiated TH17 cells. We provide evidence that BET controls TH17 differentiation in a bromodomain-dependent manner through a mechanism that includes the direct regulation of multiple effector TH17-associated cytokines, including IL17, IL21 and GMCSF. We also demonstrate that BET family members Brd2 and Brd4 associate with the Il17 locus in TH17 cells, and that this association requires bromodomains. We recapitulate the critical role of BET bromodomains in TH17 differentiation in vivo and show that therapeutic dosing of the BET inhibitor is efficacious in mouse models of autoimmunity. Our results identify the BET family of proteins as a fundamental link between chromatin signaling and TH17 biology, and support the notion of BET inhibition as a point of therapeutic intervention in autoimmune conditions. 4 samples were analyzed: two conditions in duplicate. Naive T cells were placed in conditions leading to TH17 differentiation, with and without BET inhibitor. RNA was collected at 48 hours.
2013-09-20 | E-GEOD-37270 | biostudies-arrayexpress
Project description: Not available
| S-EPMC5519619 | biostudies-literature
Project description: Not available
| S-EPMC6930085 | biostudies-literature
Project description:There is evidence that microglia interact with infiltrating Th1 and Th17 cells and this interaction results in mutual activation. However, the potential of a distinct cytokine milieu generated by these effector T cell subsets to activate microglia is poorly understood. In this study, we tested the ability of factors secreted by Th1 and Th17 cells to induce microglial activation. Interestingly, we found that only Th1-associated factors had the potential to activate microglia while the Th17-associated factors as well as direct contact of Th17 cells with microglia only had a minimal effect. Further Th1-derived factors triggered a proinflammatory M1-type gene expression profile in microglia Microglia harvested from mixed glial cultures were treated with supernatants from Th1- or Th17 cultures. Microglia cultured in medium was used as controls. At 16h post treatment RNA was isolated from the microglia and probed on Agilent´s murine 4x44k microarrays. RNA isolated from four independent experiments were used for the gene expression profiling. Microglia, Th1, Th17
2013-12-31 | E-GEOD-45384 | biostudies-arrayexpress
Project description: Not available
| S-EPMC2792038 | biostudies-literature
Project description:Staphylococcus aureus is a highly adaptable human pathogen; therefore a constant search for new effective antibiotic compounds is being preformed. Gene expression profiling can be used to determine potential targets and mechanisms of action (MOA) of known or potential drugs. The goal of our study was a development of a focused transcriptome platform to be used for confirming the MOA of new chemical entities which are designed as inhibitors of Mur ligases. A model transcriptional profile was set up for well described inhibitor of MurA ligase, fosfomycin. Moreover, we wanted to identify the pathways and processes primarily affected by this compound. S. aureus ATCC 29213 cells were treated with low concentrations of fosfomycin (1 and 4 µg/ml, respectively) and harvested at 10, 20 and 40 minutes after treatment, respectively. RNA was isolated, transcribed, labeled and hybridized to S. aureus GeneChips, representing approximately 3000 S. aureus genes. Using meta-analysis of our results and the results in the S. aureus microarray database, we have confirmed that fosfomycin induces “cell wall stimulon” genes and were able to identify genes and pathways specifically modulated by fosfomycin.
2009-03-26 | GSE15394 | GEO