Microarray gene expression data from sorted lung epithelial cells during heterotypic immunity
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE128897 | GEO | 2020/03/16
REPOSITORIES: GEO
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Project description:BACKGROUND: Streptococcus pneumoniae, the pneumococcus, is the main etiological agent of pneumonia. Pneumococcal infection is initiated by bacterial adherence to lung epithelial cells. The exact transcriptional changes occurring in both host and microbe during infection are unknown. Here, we developed a time-resolved infection model of human lung alveolar epithelial cells by S. pneumoniae and assess the resulting transcriptome changes in both organisms simultaneously by using dual RNA-seq. RESULTS: Functional analysis of the time-resolved dual RNA-seq data identifies several features of pneumococcal infection. For instance, we show that the glutathione-dependent reactive oxygen detoxification pathway in epithelial cells is activated by reactive oxygen species produced by S. pneumoniae. Addition of the antioxidant resveratrol during infection abates this response. At the same time, pneumococci activate the competence regulon during co-incubation with lung epithelial cells. By comparing transcriptional changes between wild-type encapsulated and mutant unencapsulated pneumococci, we demonstrate that adherent pneumococci, but not free-floating bacteria, repress innate immune responses in epithelial cells including expression of the chemokine IL-8 and the production of antimicrobial peptides. We also show that pneumococci activate several sugar transporters in response to adherence to epithelial cells and demonstrate that this activation depends on host-derived mucins. CONCLUSIONS: We provide a dual-transcriptomics overview of early pneumococcal infection in a time-resolved manner, providing new insights into host-microbe interactions. To allow easy access to the data by the community, a web-based platform was developed ( http://dualrnaseq.molgenrug.nl ). Further database exploration may expand our understanding of epithelial-pneumococcal interaction, leading to novel antimicrobial strategies.
2016-08-26 | GSE79595 | GEO
Project description:Rationale: Respiratory syncytial virus (RSV) and Streptococcus pneumoniae are major respiratory pathogens. Co-infection with RSV and S. pneumoniae is associated with severe and often fatal pneumonia but the molecular basis for this remains unclear. Objectives: To determine if interaction between RSV and pneumococci enhances pneumococcal virulence. Methods: We used confocal microscopy and western blot to identify the receptors involved in direct binding of RSV and pneumococci, the effects of which were studied in both in vivo and in vitro models of infection. Human ciliated respiratory epithelial cell cultures were infected with RSV for 72h and then challenged with pneumococci. Pneumococci were collected after 2h exposure and changes in gene expression determined using qRT-PCR. Results: Following incubation with RSV or purified G protein, pneumococci demonstrated a significant increase in the inflammatory response and bacterial adherence to human ciliated epithelial cultures and markedly increased virulence in a pneumonia model in mice. This was associated with extensive changes in the pneumococcal transcriptome and significant upregulation in the expression of key pneumococcal virulence genes, including the gene for the pneumococcal toxin, pneumolysin. We show that mechanistically this is due to RSV G glycoprotein binding penicillin binding protein 1a. Conclusion: The direct interaction between a respiratory virus protein and the pneumococcus resulting in increased bacterial virulence and worsening disease outcome is a new paradigm in respiratory infection.
2014-06-21 | GSE58424 | GEO
Project description:Rationale: Respiratory syncytial virus (RSV) and Streptococcus pneumoniae are major respiratory pathogens. Co-infection with RSV and S. pneumoniae is associated with severe and often fatal pneumonia but the molecular basis for this remains unclear. Objectives: To determine if interaction between RSV and pneumococci enhances pneumococcal virulence. Methods: We used confocal microscopy and western blot to identify the receptors involved in direct binding of RSV and pneumococci, the effects of which were studied in both in vivo and in vitro models of infection. Human ciliated respiratory epithelial cell cultures were infected with RSV for 72h and then challenged with pneumococci. Pneumococci were collected after 2h exposure and changes in gene expression determined using qRT-PCR. Results: Following incubation with RSV or purified G protein, pneumococci demonstrated a significant increase in the inflammatory response and bacterial adherence to human ciliated epithelial cultures and markedly increased virulence in a pneumonia model in mice. This was associated with extensive changes in the pneumococcal transcriptome and significant upregulation in the expression of key pneumococcal virulence genes, including the gene for the pneumococcal toxin, pneumolysin. We show that mechanistically this is due to RSV G glycoprotein binding penicillin binding protein 1a. Conclusion: The direct interaction between a respiratory virus protein and the pneumococcus resulting in increased bacterial virulence and worsening disease outcome is a new paradigm in respiratory infection.
2014-06-21 | GSE58425 | GEO
Project description:Microarray gene expression data from sorted lung epithelial cells during heterotypic immunity
| PRJNA529239 | ENA
Project description:CD4+ tissue-resident memory T cells (TRM) drive tissue-specific chronic inflammation by expressing characteristic functional molecules, but how tissue microenvironment-derived stimuli orchestrate their characteristics remains unclear. We found that intracellular hypoxia-dependent activation of EPAS1 programmed human and mouse type 2 CD4+ TRM to acquire immunoregulatory properties through the upregulation of CTLA-4 and IL-10. Genetic deletion of Epas1 in CD4+ T cells decreases the expression of immunoregulatory molecules in type 2 CD4+ TRM, consequently exacerbating lung inflammation. Spatial transcriptomic profiling of human asthmatic lungs identified FOXP3-negative CTLA4+GATA3+ TRM cells with activated hypoxic gene signatures in tertiary lymphoid structures. Our findings revealed that hypoxic pathway activation is a critical determinant of type 2 CD4+ TRM characteristics and highlight Epas1-dependent pathways as promising targets for treating chronic inflammatory disorders.
2026-03-30 | GSE320590 | GEO
Project description:CD4+ tissue-resident memory T cells (TRM) drive tissue-specific chronic inflammation by expressing characteristic functional molecules, but how tissue microenvironment-derived stimuli orchestrate their characteristics remains unclear. We found that intracellular hypoxia-dependent activation of EPAS1 programmed human and mouse type 2 CD4+ TRM to acquire immunoregulatory properties through the upregulation of CTLA-4 and IL-10. Genetic deletion of Epas1 in CD4+ T cells decreases the expression of immunoregulatory molecules in type 2 CD4+ TRM, consequently exacerbating lung inflammation. Spatial transcriptomic profiling of human asthmatic lungs identified FOXP3-negative CTLA4+GATA3+ TRM cells with activated hypoxic gene signatures in tertiary lymphoid structures. Our findings revealed that hypoxic pathway activation is a critical determinant of type 2 CD4+ TRM characteristics and highlight Epas1-dependent pathways as promising targets for treating chronic inflammatory disorders.
2026-03-30 | GSE320588 | GEO
Project description:CD4+ tissue-resident memory T cells (TRM) drive tissue-specific chronic inflammation by expressing characteristic functional molecules, but how tissue microenvironment-derived stimuli orchestrate their characteristics remains unclear. We found that intracellular hypoxia-dependent activation of EPAS1 programmed human and mouse type 2 CD4+ TRM to acquire immunoregulatory properties through the upregulation of CTLA-4 and IL-10. Genetic deletion of Epas1 in CD4+ T cells decreases the expression of immunoregulatory molecules in type 2 CD4+ TRM, consequently exacerbating lung inflammation. Spatial transcriptomic profiling of human asthmatic lungs identified FOXP3-negative CTLA4+GATA3+ TRM cells with activated hypoxic gene signatures in tertiary lymphoid structures. Our findings revealed that hypoxic pathway activation is a critical determinant of type 2 CD4+ TRM characteristics and highlight Epas1-dependent pathways as promising targets for treating chronic inflammatory disorders.
2026-03-30 | GSE320591 | GEO
Project description:CD4+ tissue-resident memory T cells (TRM) drive tissue-specific chronic inflammation by expressing characteristic functional molecules, but how tissue microenvironment-derived stimuli orchestrate their characteristics remains unclear. We found that intracellular hypoxia-dependent activation of EPAS1 programmed human and mouse type 2 CD4+ TRM to acquire immunoregulatory properties through the upregulation of CTLA-4 and IL-10. Genetic deletion of Epas1 in CD4+ T cells decreases the expression of immunoregulatory molecules in type 2 CD4+ TRM, consequently exacerbating lung inflammation. Spatial transcriptomic profiling of human asthmatic lungs identified FOXP3-negative CTLA4+GATA3+ TRM cells with activated hypoxic gene signatures in tertiary lymphoid structures. Our findings revealed that hypoxic pathway activation is a critical determinant of type 2 CD4+ TRM characteristics and highlight Epas1-dependent pathways as promising targets for treating chronic inflammatory disorders.
2026-03-30 | GSE320592 | GEO
Project description:Rationale: Respiratory syncytial virus (RSV) and Streptococcus pneumoniae are major respiratory pathogens. Co-infection with RSV and S. pneumoniae is associated with severe and often fatal pneumonia but the molecular basis for this remains unclear. Objectives: To determine if interaction between RSV and pneumococci enhances pneumococcal virulence. Methods: We used confocal microscopy and western blot to identify the receptors involved in direct binding of RSV and pneumococci, the effects of which were studied in both in vivo and in vitro models of infection. Human ciliated respiratory epithelial cell cultures were infected with RSV for 72h and then challenged with pneumococci. Pneumococci were collected after 2h exposure and changes in gene expression determined using qRT-PCR. Results: Following incubation with RSV or purified G protein, pneumococci demonstrated a significant increase in the inflammatory response and bacterial adherence to human ciliated epithelial cultures and markedly increased virulence in a pneumonia model in mice. This was associated with extensive changes in the pneumococcal transcriptome and significant upregulation in the expression of key pneumococcal virulence genes, including the gene for the pneumococcal toxin, pneumolysin. We show that mechanistically this is due to RSV G glycoprotein binding penicillin binding protein 1a. Conclusion: The direct interaction between a respiratory virus protein and the pneumococcus resulting in increased bacterial virulence and worsening disease outcome is a new paradigm in respiratory infection. Comparison of the Streptococcus pneumoniae D39 RSV treated compared to BSA Treated in BEBM medium One condition design comparision of two strains including a dye swap
2014-06-21 | E-GEOD-58425 | biostudies-arrayexpress
Project description:Rationale: Respiratory syncytial virus (RSV) and Streptococcus pneumoniae are major respiratory pathogens. Co-infection with RSV and S. pneumoniae is associated with severe and often fatal pneumonia but the molecular basis for this remains unclear. Objectives: To determine if interaction between RSV and pneumococci enhances pneumococcal virulence. Methods: We used confocal microscopy and western blot to identify the receptors involved in direct binding of RSV and pneumococci, the effects of which were studied in both in vivo and in vitro models of infection. Human ciliated respiratory epithelial cell cultures were infected with RSV for 72h and then challenged with pneumococci. Pneumococci were collected after 2h exposure and changes in gene expression determined using qRT-PCR. Results: Following incubation with RSV or purified G protein, pneumococci demonstrated a significant increase in the inflammatory response and bacterial adherence to human ciliated epithelial cultures and markedly increased virulence in a pneumonia model in mice. This was associated with extensive changes in the pneumococcal transcriptome and significant upregulation in the expression of key pneumococcal virulence genes, including the gene for the pneumococcal toxin, pneumolysin. We show that mechanistically this is due to RSV G glycoprotein binding penicillin binding protein 1a. Conclusion: The direct interaction between a respiratory virus protein and the pneumococcus resulting in increased bacterial virulence and worsening disease outcome is a new paradigm in respiratory infection. Comparison of the Streptococcus pneumoniae D39 Protein P treated compared to Protein GTreated in BEBM medium One condition design comparision of two strains including a dye swap
2014-06-21 | E-GEOD-58424 | biostudies-arrayexpress