Histone H3 Acetylation and microRNA(s) Regulate Inflammatory response in Mastitis Mice, induced by Staphylococcus aureus Infection
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE54232 | GEO | 2014/06/01
SECONDARY ACCESSION(S): PRJNA235991
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-06-01 | E-GEOD-54232 | biostudies-arrayexpress
Project description:Bacterial infection in the mammary gland parenchyma induces local inflammation that can lead to a multietiological complex disease called mastitis. Globally Staphylococcus aureus is the single largest mastitis pathogen and the infection can ultimately result in either subclinical or chronic and sometimes lifelong infection. In the present report we have addressed the differential inflammatory response in the mice mammary tissue during intramammary infection and the altered epigenetic context induced by two closely related strains of S. aureus. Immunohistochemical and immunoblot analysis showed strain specific hyperacetylation at histone H3K9 and H3K14 residues. Real-time PCR and genome-wide gene expression studied showed expression of a set of proinflammatory genes and cytokines in a temporal manner. Remarkably, over expression of the genes significantly correlated with the promoter specific acetylation in these residues. Furthermore, we have identified several differentially expressed known miRNAs and 4 novel miRNAs in the S. aureus infected mice mammary tissue by small RNA sequencing. By employing these gene expression data, an attempt has been made to delineate the gene regulatory networks in the strain specific inflammatory response. Apparently, one of the isolates of S. aureus activated the NFkB signaling leading to drastic inflammatory response and induction of immune surveillance, which could lead to rapid clearance of the pathogen. The other strain repressed most of the inflammatory response, which might help in its sustenance in the host tissue. Taken together, our studies shed substantial lights to understand the mechanisms of strain specific differential inflammatory response to S. aureus infection during mastitis. 3 samples in two biological replicates. One control and two samples infected with two different strains of S. aureus
2014-06-01 | E-GEOD-54230 | biostudies-arrayexpress
Project description:Bacterial infection in the mammary gland parenchyma induces local inflammation that can lead to a multietiological complex disease called mastitis. Globally Staphylococcus aureus is the single largest mastitis pathogen and the infection can ultimately result in either subclinical or chronic and sometimes lifelong infection. In the present report we have addressed the differential inflammatory response in the mice mammary tissue during intramammary infection and the altered epigenetic context induced by two closely related strains of S. aureus. Immunohistochemical and immunoblot analysis showed strain specific hyperacetylation at histone H3K9 and H3K14 residues. Real-time PCR and genome-wide gene expression studied showed expression of a set of proinflammatory genes and cytokines in a temporal manner. Remarkably, over expression of the genes significantly correlated with the promoter specific acetylation in these residues. Furthermore, we have identified several differentially expressed known miRNAs and 4 novel miRNAs in the S. aureus infected mice mammary tissue by small RNA sequencing. By employing these gene expression data, an attempt has been made to delineate the gene regulatory networks in the strain specific inflammatory response. Apparently, one of the isolates of S. aureus activated the NFkB signaling leading to drastic inflammatory response and induction of immune surveillance, which could lead to rapid clearance of the pathogen. The other strain repressed most of the inflammatory response, which might help in its sustenance in the host tissue. Taken together, our studies shed substantial lights to understand the mechanisms of strain specific differential inflammatory response to S. aureus infection during mastitis.
2014-06-01 | GSE54230 | GEO
Project description:Bacterial infection in the mammary gland parenchyma induces local inflammation that can lead to a multietiological complex disease called mastitis. Globally Staphylococcus aureus is the single largest mastitis pathogen and the infection can ultimately result in either subclinical or chronic and sometimes lifelong infection. In the present report we have addressed the differential inflammatory response in the mice mammary tissue during intramammary infection and the altered epigenetic context induced by two closely related strains of S. aureus. Immunohistochemical and immunoblot analysis showed strain specific hyperacetylation at histone H3K9 and H3K14 residues. Real-time PCR and genome-wide gene expression studied showed expression of a set of proinflammatory genes and cytokines in a temporal manner. Remarkably, over expression of the genes significantly correlated with the promoter specific acetylation in these residues. Furthermore, we have identified several differentially expressed known miRNAs and 4 novel miRNAs in the S. aureus infected mice mammary tissue by small RNA sequencing. By employing these gene expression data, an attempt has been made to delineate the gene regulatory networks in the strain specific inflammatory response. Apparently, one of the isolates of S. aureus activated the NFkB signaling leading to drastic inflammatory response and induction of immune surveillance, which could lead to rapid clearance of the pathogen. The other strain repressed most of the inflammatory response, which might help in its sustenance in the host tissue. Taken together, our studies shed substantial lights to understand the mechanisms of strain specific differential inflammatory response to S. aureus infection during mastitis. One control and two samples infected with two different strains of S. aureus
2014-06-01 | E-GEOD-54231 | biostudies-arrayexpress
Project description:Bacterial infection in the mammary gland parenchyma induces local inflammation that can lead to a multietiological complex disease called mastitis. Globally Staphylococcus aureus is the single largest mastitis pathogen and the infection can ultimately result in either subclinical or chronic and sometimes lifelong infection. In the present report we have addressed the differential inflammatory response in the mice mammary tissue during intramammary infection and the altered epigenetic context induced by two closely related strains of S. aureus. Immunohistochemical and immunoblot analysis showed strain specific hyperacetylation at histone H3K9 and H3K14 residues. Real-time PCR and genome-wide gene expression studied showed expression of a set of proinflammatory genes and cytokines in a temporal manner. Remarkably, over expression of the genes significantly correlated with the promoter specific acetylation in these residues. Furthermore, we have identified several differentially expressed known miRNAs and 4 novel miRNAs in the S. aureus infected mice mammary tissue by small RNA sequencing. By employing these gene expression data, an attempt has been made to delineate the gene regulatory networks in the strain specific inflammatory response. Apparently, one of the isolates of S. aureus activated the NFkB signaling leading to drastic inflammatory response and induction of immune surveillance, which could lead to rapid clearance of the pathogen. The other strain repressed most of the inflammatory response, which might help in its sustenance in the host tissue. Taken together, our studies shed substantial lights to understand the mechanisms of strain specific differential inflammatory response to S. aureus infection during mastitis.
2014-06-01 | GSE54231 | GEO
Project description:BackgroundThere is renewed interest towards understanding the host-pathogen interaction in the light of epigenetic modifications. Although epithelial tissue is the major site for host-pathogen interactions, there is handful of studies to show how epithelial cells respond to pathogens. Bacterial infection in the mammary gland parenchyma induces local and subsequently systemic inflammation that results in a complex disease called mastitis. Globally Staphylococcus aureus is the single largest mastitis pathogen and the infection can ultimately result in either subclinical or chronic and sometimes lifelong infection.ResultsIn the present report we have addressed the differential inflammatory response in mice mammary tissue during intramammary infection and the altered epigenetic context induced by two closely related strains of S. aureus, isolated from field samples. Immunohistochemical and immunoblotting analysis showed strain specific hyperacetylation at histone H3K9 and H3K14 residues. Global gene expression analysis in S. aureus infected mice mammary tissue revealed a selective set of upregulated genes that significantly correlated with the promoter specific, histone H3K14 acetylation. Furthermore, we have identified several differentially expressed known miRNAs and 3 novel miRNAs in S. aureus infected mice mammary tissue by small RNA sequencing. By employing these gene expression data, an attempt has been made to delineate the gene regulatory networks in the strain specific inflammatory response. Apparently, one of the isolates of S. aureus activated the NF-κB signaling leading to drastic inflammatory response and induction of immune surveillance, which could possibly lead to rapid clearance of the pathogen. The other strain repressed most of the inflammatory response, which might help in its sustenance in the host tissue.ConclusionTaken together, our studies shed substantial lights to understand the mechanisms of strain specific differential inflammatory response to S. aureus infection during mastitis. In a broader perspective this study also paves the way to understand how certain bacteria can evade the immune surveillance and cause sustained infection while others are rapidly cleared from the host body.
| S-EPMC4114167 | biostudies-literature
Project description:BackgroundS. aureus is one of the major etiological agents causing bovine subclinical mastitis. The regulatory effects of H3K27me3 on gene expression in subclinical S. aureus mastitis cows are unknown. This study aimed to profile genome-wide transcriptional changes regulated by H3K27me3 in bovine lymphocytes applied in subclinical S. aureus mastitis cows and healthy controls.ResultsA total of 61 differentially expressed genes (DEGs) were detected in subclinical S. aureus mastitis cows compared to the healthy controls, of which 25 DEGs are up-regulated and the rest are down-regulated genes in subclinical S.aureus mastitis cows. The up-regulated genes are mainly involved in the Jak-STAT signaling pathway, cytokine-cytokine receptor interaction, and T cell receptor-signaling pathway, while the down-regulated genes are related to metabolism pathways. Combination analysis of histone methylation and gene expression revealed that H3K27 trimethylation levels in silent genes were higher in subclinical S. aureus mastitis cattle than in healthy cows. The key regions of H3K27me3 target genes related to subclinical S. aureus mastitis were the upstream 2 kb regions of the DEGs relative to transcription start site (TSS).ConclusionsThe current study provides a novel insight into the interaction between S. aureus and lymphocytes in lactating cows by histone H3 methylation regulation. The differentially expressed genes in bovine lymphocytes regulated by H3K27me3 on upstream 2 kb regions (IL10, PTX3 and etc.) may relate to S. aureus mastitis susceptibility and could be considered as key candidate genes for anti- S. aureus mastitis study and breeding.
| S-EPMC4977872 | biostudies-literature
Project description:Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) are the most common pathogens of mastitis, and S. aureus generally causes subclinical mastitis which is more persistent and resistant to treatment. Peptidoglycan (PGN) and lipoteichoic acid (LTA) are cell wall components of S. aureus. Although the roles of PGN and LTA in causing inflammation are well studied, the epigenetic mechanisms of the effects of PGN and LTA on the inflammation and lactation remain poorly understood. This study characterized the gene expression profiling by RNA sequencing and investigated DNA methylation and histone acetylation in relation to inflammation and lactation in the immortalized bovine mammary epithelial cell line (MAC-T). The cells were cultured for 24 h with neither PGN nor LTA (CON), PGN (30 ?g/mL), LTA (30 ?g/mL), and PGN (30 ?g/mL) + LTA (30 ?g/mL), respectively. The number of differentially expressed genes (DEGs) and the expression of proinflammatory factors including interleukin (IL)-1?, IL-6, IL-8, chemokine (C-X-C motif) ligand (CXCL)1, and CXCL6 of the treatments increased in the following order: CON < PGN < LTA < PGN + LTA, and the DEGs mainly enriched on the cytokine-cytokine receptor interaction and chemokine signaling pathway. LTA and PGN + LTA induced hypomethylation of global DNA by suppressing DNA methyltransferase (DNMT) activity. PGN and LTA, alone or combined, decreased the mRNA expression of casein genes (CSN1S1, CSN2, and CSN3) and the expression of two caseins (CSN2 and CSN3), and reduced histone H3 acetylation by suppressing histone acetyltransferase (HAT) activity and promoting histone deacetylase (HDAC) activity. Collectively, this study revealed that PGN and LTA induced inflammation probably due to decreasing DNA methylation through regulating DNMT activity, and decreased lactation possibly through reducing histone H3 acetylation by regulating HAT and HDAC activity in bovine mammary epithelial cells.
| S-EPMC7232188 | biostudies-literature
Project description:Acetylation of histone H3 on lysine 56 occurs during mitotic and meiotic S phase in fungal species. This acetylation blocks a direct electrostatic interaction between histone H3 and nucleosomal DNA, and the absence of this modification is associated with extreme sensitivity to genotoxic agents. We show here that H3-K56 acetylation is catalyzed when Rtt109, a protein that lacks significant homology to known acetyltransferases, forms an active complex with either of two histone binding proteins, Asf1 or Vps75. Rtt109 binds to both these cofactors, but not to histones alone, forming enzyme complexes with kinetic parameters similar to those of known histone acetyltransferase (HAT) enzymes. Therefore, H3-K56 acetylation is catalyzed by a previously unknown mechanism that requires a complex of two proteins: Rtt109 and a histone chaperone. Additionally, these complexes are functionally distinct, with the Rtt109/Asf1 complex, but not the Rtt109/Vps75 complex, being critical for resistance to genotoxic agents.
| S-EPMC1853276 | biostudies-literature
Project description:S. aureus is one of the main pathogens involved in ruminant mastitis worldwide. The severity of staphylococcal infection is highly variable, ranging from subclinical to gangrenous mastitis. This work represents an in-depth characterization of S. aureus mastitis isolates to identify bacterial factors involved in severity of mastitis infection.We employed genomic, transcriptomic and proteomic approaches to comprehensively compare two clonally related S. aureus strains that reproducibly induce severe (strain O11) and milder (strain O46) mastitis in ewes. Variation in the content of mobile genetic elements, iron acquisition and metabolism, transcriptional regulation and exoprotein production was observed. In particular, O11 produced relatively high levels of exoproteins, including toxins and proteases known to be important in virulence. A characteristic we observed in other S. aureus strains isolated from clinical mastitis cases.Our data are consistent with a dose-dependant role of some staphylococcal factors in the hypervirulence of strains isolated from severe mastitis. Mobile genetic elements, transcriptional regulators, exoproteins and iron acquisition pathways constitute good targets for further research to define the underlying mechanisms of mastitis severity.
| S-EPMC3214034 | biostudies-literature