Pathogen-specific innate immune response patterns are distinctly affected by genetic diversity
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE177040 | GEO | 2022/03/03
REPOSITORIES: GEO
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Project description:Initial transcriptional response of human peripheral monocytes infected with a set of three gram-positive bacterial pathogens (Listeria monocytogenes, Staphylococcus aureus and Streptococcus pneumoniae). Monocytes were isolated from five probands.
2008-12-08 | E-MEXP-1613 | biostudies-arrayexpress
Project description:Pneumonia is a serious problem worldwide. We recently demonstrated that innate defense mechanisms of the lung are highly inducible against pneumococcal pneumonia. To determine the breadth of protection conferred by stimulation of lung mucosal innate immunity, and to identify cells and signaling pathways activated by this treatment, mice were treated with an aerosolized bacterial lysate, then challenged with lethal doses of bacterial and fungal pathogens. Mice were highly protected against a broad array of Gram-positive, Gram-negative, and Class A bioterror bacterial pathogens, and Aspergillus fumigatus. Protection was associated with rapid pathogen killing within the lungs, and this effect was recapitulated in vitro using a respiratory epithelial cell line. Gene expression analysis of lung tissue showed marked activation of NF-kappa-B, Type I and II interferon, and antifungal Card9-Bcl10-Malt1 pathways. Cytokines were the most strongly induced genes, but the inflammatory cytokines TNF and IL-6 were not required for protection. Lung-expressed antimicrobial peptides were also highly upregulated. Taken together, stimulated innate resistance (StIR) appears to occur through the activation of multiple host defense signaling pathways in lung epithelial cells, inducing rapid pathogen killing, and conferring broad protection against virulent bacterial and fungal pathogens. Augmentation of innate antimicrobial defenses of the lungs might have therapeutic value for protection of patients with neutropenia or impaired adaptive immunity against opportunistic pneumonia, and for defense of immunocompetent subjects against a bioterror threat or epidemic respiratory infection. Keywords: Differential expression, innate immunity, pneumonia, immunocompromised host; lung epithelium, in vitro, MLE-15 cells were treated with sham (PBS), NTHi lysate (100 ug/ml) or EF2505-III (40 ug/ml). 4 unique samples per group. Treated for 2 hours. Hybridized to Illumina Sentrix Mouse-6 v1.1 Beadhips.
2010-06-24 | E-GEOD-13685 | biostudies-arrayexpress
Project description:Pneumonia is a serious problem worldwide. We recently demonstrated that innate defense mechanisms of the lung are highly inducible against pneumococcal pneumonia. To determine the breadth of protection conferred by stimulation of lung mucosal innate immunity, and to identify cells and signaling pathways activated by this treatment, mice were treated with an aerosolized bacterial lysate, then challenged with lethal doses of bacterial and fungal pathogens. Mice were highly protected against a broad array of Gram-positive, Gram-negative, and Class A bioterror bacterial pathogens, and Aspergillus fumigatus. Protection was associated with rapid pathogen killing within the lungs, and this effect was recapitulated in vitro using a respiratory epithelial cell line. Gene expression analysis of lung tissue showed marked activation of NF-kappaB, Type I and II interferon, and antifungal Card9-Bcl10-Malt1 pathways. Cytokines were the most strongly induced genes, but the inflammatory cytokines TNF and IL-6 were not required for protection. Lung-expressed antimicrobial peptides were also highly upregulated. Taken together, stimulated innate resistance (StIR) appears to occur through the activation of multiple host defense signaling pathways in lung epithelial cells, inducing rapid pathogen killing, and conferring broad protection against virulent bacterial and fungal pathogens. Augmentation of innate antimicrobial defenses of the lungs might have therapeutic value for protection of patients with neutropenia or impaired adaptive immunity against opportunistic pneumonia, and for defense of immunocompetent subjects against a bioterror threat or epidemic respiratory infection. Keywords: differential gene expression; time course; innate immunity; pneumonia; immunocompromised host; lung epithelium Gene expression patterns in mouse lung homogenates were analyzed 2h after exposure to aerosolized PBS (Sham treatment), 2h after exposure to aerosolized NTHi lysate or 4h after exposure to aerosolized NTHi lysate. Each group consisted of six mice.
2010-06-24 | E-GEOD-13740 | biostudies-arrayexpress
Project description:Pneumonia is a serious problem worldwide. We recently demonstrated that innate defense mechanisms of the lung are highly inducible against pneumococcal pneumonia. To determine the breadth of protection conferred by stimulation of lung mucosal innate immunity, and to identify cells and signaling pathways activated by this treatment, mice were treated with an aerosolized bacterial lysate, then challenged with lethal doses of bacterial and fungal pathogens. Mice were highly protected against a broad array of Gram-positive, Gram-negative, and Class A bioterror bacterial pathogens, and Aspergillus fumigatus. Protection was associated with rapid pathogen killing within the lungs, and this effect was recapitulated in vitro using a respiratory epithelial cell line. Gene expression analysis of lung tissue showed marked activation of NF-kappaB, Type I and II interferon, and antifungal Card9-Bcl10-Malt1 pathways. Cytokines were the most strongly induced genes, but the inflammatory cytokines TNF and IL-6 were not required for protection. Lung-expressed antimicrobial peptides were also highly upregulated. Taken together, stimulated innate resistance (StIR) appears to occur through the activation of multiple host defense signaling pathways in lung epithelial cells, inducing rapid pathogen killing, and conferring broad protection against virulent bacterial and fungal pathogens. Augmentation of innate antimicrobial defenses of the lungs might have therapeutic value for protection of patients with neutropenia or impaired adaptive immunity against opportunistic pneumonia, and for defense of immunocompetent subjects against a bioterror threat or epidemic respiratory infection. Keywords: differential gene expression; time course; innate immunity; pneumonia; immunocompromised host; lung epithelium
2008-11-26 | GSE13740 | GEO
Project description:Pneumonia is a serious problem worldwide. We recently demonstrated that innate defense mechanisms of the lung are highly inducible against pneumococcal pneumonia. To determine the breadth of protection conferred by stimulation of lung mucosal innate immunity, and to identify cells and signaling pathways activated by this treatment, mice were treated with an aerosolized bacterial lysate, then challenged with lethal doses of bacterial and fungal pathogens. Mice were highly protected against a broad array of Gram-positive, Gram-negative, and Class A bioterror bacterial pathogens, and Aspergillus fumigatus. Protection was associated with rapid pathogen killing within the lungs, and this effect was recapitulated in vitro using a respiratory epithelial cell line. Gene expression analysis of lung tissue showed marked activation of NF-kappa-B, Type I and II interferon, and antifungal Card9-Bcl10-Malt1 pathways. Cytokines were the most strongly induced genes, but the inflammatory cytokines TNF and IL-6 were not required for protection. Lung-expressed antimicrobial peptides were also highly upregulated. Taken together, stimulated innate resistance (StIR) appears to occur through the activation of multiple host defense signaling pathways in lung epithelial cells, inducing rapid pathogen killing, and conferring broad protection against virulent bacterial and fungal pathogens. Augmentation of innate antimicrobial defenses of the lungs might have therapeutic value for protection of patients with neutropenia or impaired adaptive immunity against opportunistic pneumonia, and for defense of immunocompetent subjects against a bioterror threat or epidemic respiratory infection. Keywords: Differential expression, innate immunity, pneumonia, immunocompromised host; lung epithelium, in vitro,
2008-11-21 | GSE13685 | GEO
Project description:Sepsis is a clinical syndrome that can be caused by bacteria or fungi. Early knowledge on the nature of the causative agent is a prerequisite for targeted anti-microbial therapy. Besides currently used detection methods like blood culture and PCR-based assays, the analysis of the transcriptional response of the host to infecting organisms holds great promise. In this study, we aim to examine the transcriptional footprint of infections caused by the bacterial pathogens Staphylococcus aureus and Escherichia coli and the fungal pathogens Candida albicans and Aspergillus fumigatus in a human whole-blood model. Moreover, we use the expression information to build a random forest classifier to determine if the pathogen is bacterial, fungal or neither of the two. After normalizing the transcription intensities using stably expressed reference genes, we filtered the gene set for biomarkers of bacterial or fungal blood infections. This selection is based on differential expression and an additional gene relevance measure. In this way, we identified 38 biomarker genes, including IL6, SOCS3, and IRG1 which were already associated to sepsis by other studies. Using these genes, we trained the classifier and assessed its performance. It yielded a 96% accuracy (sensitivities >93%, specificities >97%) for a 10-fold stratified cross-validation and a 92% accuracy (sensitivities and specificities >83%) for an additional dataset comprising Cryptococcus neoformans infections. Furthermore, the noise-robustness of the classifier suggests high rates of correct class predictions on datasets of new species. In conclusion, this genome-wide approach demonstrates an effective feature selection process in combination with the construction of a well-performing classification model. Further analyses of genes with pathogen-dependent expression patterns can provide insights into the systemic host responses, which may lead to new anti-microbial therapeutic advances. Analysis of innate immune activation on the basis of gene expression of whole blood cells during ex vivo whole blood infection with bacterial (Staphylococcus aureus, Escherichia coli) and fungal pathogens (Candida albicans, Aspergillus fumigatus) in comparison to mock-treated blood.
2015-03-11 | E-GEOD-65088 | biostudies-arrayexpress
Project description:To explore the circulating miRNA expression after subcutaneous injection of Gram negative and positive bacteria in the mice The recombinant specific Gram negative pathogens Escherichia coli (xen14) and Gram positive pathogens Staphyllococcus aureus (xen29) were purchased from the Caliper (Caliper, Princeton, NJ, USA). 1M-CM-^W108 Escherichia coli or Staphyllococcus aureus pathogen in 100 M-NM-<l PBS was injected subcutaneously with Fr. 25 needle into the back of the mice to cause bacterial infection of the mice. An extra group of animals was inoculated with PBS to serve as a negative control. The mice had access to food and water ad libitum both before and after bacteria injection. The mice were killed at the indicated time points (4, 8, and 24 h) after the bacteria injection, and whole blood was drawn.
2014-01-01 | E-GEOD-49189 | biostudies-arrayexpress
Project description:In vivo studies in mice have identified subsets of monocytes involved in the inflammatory response to pathogens, but their respective functions remains poorly understood. We report that human CD14+ monocytes represent functional ortholog to mouse Ly6C+ monocytes and are responsible for phagocytosis, Reactive Oxygen Species (ROS) and cytokine production in response to a broad range of pathogen associated molecular patterns (PAMP). In contrast a discrete population of CD14dim cells are ortholog to the mouse ly6C- monocytes and share their ability to patrol the endothelium of blood vessels, but do not produce ROS, are weak phagocytes, and poorly respond to bacterial PAMPs. Instead, CD14dim monocytes are critical for production of pro-apoptotic and pro-inflammatory cytokines in response to viruses and nucleic acids via a unique TLR7-8/MyD88/MEK pathway, while they may also contribute to tissue damage in autoimmune diseases such as Lupus.
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2022-06-03 | GSE196683 | GEO
Project description:The extensively studied intracellular pathogen, L. monocytogenes, is an ideal model for identifying small-molecule agents for treating bacterial infections. By selecting specific biological targets in L. monocytogenes, which are common to Gram-positive pathogens, we could extrapolate drug discovery information derived from this well-studied bacterium. Attenuating the pathogen’s virulence and stress response attributes without killing it, eliminates selective pressure caused by disruption of essential gene functions (as done by current antibiotics) and reduces the likelihood of developing microbes that are impervious to the effects of antibiotics. To this end, we have assessed multiple libraries of small organic compounds to identify inhibitors of L. monocytogenes σB, the alternative sigma factor common to several clinically relevant Gram-positive pathogens, such as Staphylococcus aureus, Bacillus cereus, and Bacillus anthracis. The role of σB as a transcriptional regulator of stress response and virulence makes it an ideal, well conserved target for chemotherapeutic development.
2011-12-06 | GSE16887 | GEO