Mycobacterium abscessus -bronchial epithelial cells cross-talk through Type I interferon signaling
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ABSTRACT:
PROVIDER: PRJNA589742 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10461331.fastq.gz | Fastqsanger.gz | |||
| SRR10461332.fastq.gz | Fastqsanger.gz | |||
| SRR10461333.fastq.gz | Fastqsanger.gz | |||
| SRR10461334.fastq.gz | Fastqsanger.gz | |||
| SRR10461335.fastq.gz | Fastqsanger.gz |
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Project description:Introduction: Mycobacteria are aerobic non-motile organisms with lipid rich, hydrophobic cell walls that render them resistant to antibiotics. While there are over 150 different species of NTM, Mycobacterium avium complex (MAC) and Mycobacterium abscessus (MAB) are two of the most common culprits of pulmonary infection. MAB has been found to be most common in southeastern United States (Florida to Texas) and the third most rapidly growing NTM infection. It is responsible for chronic lung infections. Mycobacterial cell wall components initiate the interaction between bacteria and host. The reaction between bronchial epithelia and components in the envelope of mycobacterial cell wall is poorly understood. Methods: A lung-on-membrane model was developed with normal human bronchial epithelial (NHBE) cells re-differentiated at the air-liquid interface (ALI) and human endothelial cells on a transwell® polyester membrane. Microparticles from MAB cell walls were developed by an inhouse protocol and added to the ALI side of lung model. NHBE cells were harvested at day 3. RNA was isolated and analyzed with RNASeq. NHBE cells were lysed and protein assay was performed with western blot. We tested whether lung INF-alpha expression would increase in mice treated with intratracheal MAB cell wall particles. A paired t-test is used to compare two population means using GraphPad Prism 7 software. Results: RNAseq analysis identified 1759 differentially expressed genes between NHBE cells challenged with and without MAB microparticles with FDR < 0.5. 410 genes had a 2.5-fold change (FC) or greater. NHBE cells exposure to MAB microparticles significantly enriched the IFN I signaling pathway. Protein overexpression of IFN I family (2'-5'-Oligoadenylate Synthetase 1, Interferon-induced GTP-binding protein Mx1, Interferon-stimulated gene 15) was found in bronchial epithelial cells following exposure to MAB cell wall microparticles. IFN-? protein and gene expressions were significantly increased in mice lung challenged with microparticles in comparison with controls. Conclusion: These data strongly support the role of Type I IFN in cross-talk between NHBE cells and MAB. They also suggest that initiating immune response by NHBE cells may play a central role in innate immunity. Furthermore, this study underscores the importance of mycobacterial cell wall in initiating innate immune response.
| S-EPMC6913194 | biostudies-literature
Project description:Bronchial Epithelial cells were exposed to microparticles generated from mycobacterium abscessus MAB cell wall per an in-house protocol. Control group was exposed to saline. Differentially expressed genes related to MAB cell wall particles were determined.
2020-08-16 | GSE140437 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-08-16 | GSE140439 | GEO
Project description:Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized as progressive and irreversible fibrosis in the interstitium of lung tissues. There is still an unmet need to develop a novel therapeutic drug for IPF. We have previously demonstrated that periostin, a matricellular protein, plays an important role in the pathogenesis of pulmonary fibrosis. However, the underlying mechanism of how periostin causes pulmonary fibrosis remains unclear. In this study, we sought to see whether the cross-talk between transforming growth factor-b (TGF-b), a central mediator in the pathogenesis of pulmonary fibrosis, and periostin in lung fibroblasts leads to generation of pulmonary fibrosis and whether taking advantage of the cross-talk between TGF-b and periostin, inhibitors for integrin aVb3, a periostin receptor, can block pulmonary fibrosis in the model mice. We found that there exists a cross-talk between TGF-b and periostin signals via aVb3/b5 converging into Smad3. This cross-talk is important for expression of several downstream molecules of TGF-b including serpin family E member 1, CCN family member 2/connective tissue growth factor, insulin-like growth factor binding protein-3, and IL-11, all of which have been already shown to be important for pulmonary fibrosis. We, moreover, found several potent integrin inhibitors to block the cross-talking with TGF-b signals and CP4715, one of the compounds, improved bleomycin-induced pulmonary fibrosis in mice. These results suggest that the cross-talk between TGF-b and periostin can be targeted for pulmonary fibrosis and that CP4715 can be a potential therapeutic agent to block the cross-talk between TGF-b and periostin.
2019-09-17 | GSE124780 | GEO
Project description:Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized as progressive and irreversible fibrosis in the interstitium of lung tissues. There is still an unmet need to develop a novel therapeutic drug for IPF. We have previously demonstrated that periostin, a matricellular protein, plays an important role in the pathogenesis of pulmonary fibrosis. However, the underlying mechanism of how periostin causes pulmonary fibrosis remains unclear. In this study, we sought to see whether the cross-talk between transforming growth factor-b (TGF-b), a central mediator in the pathogenesis of pulmonary fibrosis, and periostin in lung fibroblasts leads to generation of pulmonary fibrosis and whether taking advantage of the cross-talk between TGF-b and periostin, inhibitors for integrin aVb3, a periostin receptor, can block pulmonary fibrosis in the model mice. We found that there exists a cross-talk between TGF-b and periostin signals via aVb3/b5 converging into Smad3. This cross-talk is important for expression of several downstream molecules of TGF-b including serpin family E member 1, CCN family member 2/connective tissue growth factor, insulin-like growth factor binding protein-3, and IL-11, all of which have been already shown to be important for pulmonary fibrosis. We, moreover, found several potent integrin inhibitors to block the cross-talking with TGF-b signals and CP4715, one of the compounds, improved bleomycin-induced pulmonary fibrosis in mice. These results suggest that the cross-talk between TGF-b and periostin can be targeted for pulmonary fibrosis and that CP4715 can be a potential therapeutic agent to block the cross-talk between TGF-b and periostin.
2019-09-17 | GSE124781 | GEO
Project description:RNA from cultured human bronchial epithelial cells treated for 8 hours or for 24 hours with medium alone, interferon gamma, dexamethasone or both interferon gamma and dexamethasone. Keywords = interferon gamma Keywords = dexamethasone Keywords = human bronchial epithelial cells Keywords: dose response
2005-09-01 | GSE1815 | GEO
Project description:RNA from cultured human bronchial epithelial cells treated for 8 hours or for 24 hours with medium alone, interferon gamma, dexamethasone or both interferon gamma and dexamethasone.
2007-08-25 | E-GEOD-1815 | biostudies-arrayexpress
Project description:Mycobacterium abscessus is an opportunistic pathogen notorious for its resistance to most classes of antibiotics and low cure rates. In addition to the highly impermeable mycomembrane, M. abscessus carries an array of shared and species-specific defence mechanisms. However, it remains unknown whether M. abscessus’ antibiotic stress response is fine-tuned or an all-or-nothing response. A deeper understanding of underlying resistance and tolerance mechanisms is pivotal in development of targeted therapeutic regimens. We elucidate the transcriptomic response of M. abscessus to antibiotics recommended in treatment guidelines. The M. abscessus ATCC 19977 strain was used. Bacteria were subjected to sub-inhibitory concentrations of drugs for 4- and 24-hours, followed by RNA sequencing. In addition, time-kill kinetic analysis was performed using bacteria after pre-exposure to clarithromycin, amikacin or tigecycline for 24-hours. Lastly, Pan-genome analysis of 35 strains from all three subspecies was performed. Mycobacterium abscessus shows both drug-specific and communal transcriptomic responses to antibiotic exposure. Key features of its tolerance to antibiotics are drug-specific converting enzymes, target protection and shifts in its respiratory chain and metabolic state. The observed transcriptomic responses are likely not strain-specific, as genes involved in tolerance are found in all included strains, with the exception of erm(41) in M. abscessus subspecies massiliense. Due to the communal response elicited by ribosomal-targeting antibiotics, exposure to any of these drugs rapidly induces tolerance mechanisms that decrease susceptibility to ribosome-targeting drugs from multiple classes. Screening high-risk patients (e.g. those with bronchiectasis) for M. abscessus infection prior to starting macrolide or aminoglycoside maintenance therapy is warranted.
2022-01-25 | GSE163621 | GEO
Project description:Orthologous proteins often harbor numerous substitutions, but whether these differences result from neutral or adaptive processes is usually unclear. To tackle this challenge, we examined the divergent evolution of a model bacterial signaling pathway comprising the kinase PhoR and its cognate substrate PhoB. We show that the specificity-determining residues of these proteins are typically under purifying selection, but have, in α-proteobacteria, undergone a burst of diversification followed by extended stasis. By reversing mutations that accumulated in an α-proteobacterial PhoR, we demonstrate that these substitutions were adaptive, enabling PhoR to avoid cross-talk with a paralogous pathway that arose specifically in α-proteobacteria. Our findings demonstrate that duplication and the subsequent need to avoid cross-talk strongly influence signaling protein evolution. These results provide a concrete example of how system-wide insulation can be achieved post-duplication through a surprisingly limited number of mutations. Our work may help explain the apparent ease with which paralogous protein families expanded in all organisms. Two-condition experiment, mutant vs. WT in given growth media
2012-07-01 | E-GEOD-37545 | biostudies-arrayexpress
Project description:Orthologous proteins often harbor numerous substitutions, but whether these differences result from neutral or adaptive processes is usually unclear. To tackle this challenge, we examined the divergent evolution of a model bacterial signaling pathway comprising the kinase PhoR and its cognate substrate PhoB. We show that the specificity-determining residues of these proteins are typically under purifying selection, but have, in α-proteobacteria, undergone a burst of diversification followed by extended stasis. By reversing mutations that accumulated in an α-proteobacterial PhoR, we demonstrate that these substitutions were adaptive, enabling PhoR to avoid cross-talk with a paralogous pathway that arose specifically in α-proteobacteria. Our findings demonstrate that duplication and the subsequent need to avoid cross-talk strongly influence signaling protein evolution. These results provide a concrete example of how system-wide insulation can be achieved post-duplication through a surprisingly limited number of mutations. Our work may help explain the apparent ease with which paralogous protein families expanded in all organisms.
2012-07-02 | GSE37545 | GEO