Outbreak of pneumococcal pneumonia connected to shipyard, Finland, 2023
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ABSTRACT:
PROVIDER: PRJEB76834 | ENA |
REPOSITORIES: ENA
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Project description:Macrophage-inducible C-type lectin (Mincle) dependent sensing of pathogens trig-gers proinflammatory immune responses in professional phagocytes that contribute to protect the host against pathogen invasion. Here, we examined whether overex-pression of Mincle designed to improve early pathogen sensing by professional phagocytes would improve lung protective immunity against Streptococcus pneu-moniae in mice. Proteomic profiling of alveolar macrophages (AM) of Mincle trans-genic (tg) mice stimulated with the Mincle-specific pneumococcal ligand glucosyl-diacylglycerol (Glc-DAG) revealed increased Nlrp3 inflammasome activation and downstream IL-1 cytokine release that was not observed in Glc-DAG stimulated Mincle KO or Nlrp3 KO macrophages. Along this line, Mincle tg mice also responded with a stronger Nlrp3 expression and early proinflammatory cytokine release after challenge with S. pneumoniae, ultimately leading to fatal pneumonia in the Mincle tg mice. Importantly, Nlrp3 inhibitor treatment of Mincle tg mice significantly mitigated the observed hyperinflammatory response to pneumococcal challenge. Together, we show that overexpression of the pattern recognition receptor Mincle triggers in-creased Glc-DAG dependent Nlrp3 inflammasome activation in professional phago-cytes leading to fatal pneumococcal pneumonia in mice, which is amenable to Nlrp3 inhibitor treatment. These data show that ectopic expression of Mincle receptor con-fers increased susceptibility rather than resistance to S. pneumoniae in mice, thus highlighting the importance of an inducible Mincle receptor expression in response to microbial challenge.
2020-10-05 | PXD018752 | Pride
Project description:Rationale: Streptococcus pneumoniae is the most common bacterial cause of community acquired pneumonia. Some clinical trials have demonstrated a beneficial effect of corticosteroid therapy in community acquired pneumonia, but the mechanisms of this benefit remain unclear. Objectives: To investigate the biologic effects of corticosteroids in pneumococcal pneumonia in mice and in patients Methods: We studied lower respiratory tract transcriptomes from an observational cohort of mechanically ventilated patients and from a pneumonia model in mice. We also carried out comprehensive physiologic, biochemical, and histological analyses in mice to identify mechanisms of lung injury in S. pneumoniae with and without adjunctive steroid therapy. Measurement and Main Results: Transcriptomic analysis identified pleiotropic effects of steroid therapy on the lower respiratory tract in critically ill patients with pneumococcal pneumonia, findings that were reproducible in mice. In mice with pneumonia, dexamethasone in combination with ceftriaxone reduced (1) pulmonary edema formation, (2) alveolar protein permeability, (3) proinflammatory cytokine release, (4) histopathology lung injury score, and (5) hypoxemia, but did not increase bacterial burden. Conclusions: In combination with appropriate antibiotics in mice, treatment of pneumococcal pneumonia with steroid therapy reduces hypoxemia, pulmonary edema, lung permeability, and histologic criteria of lung injury, and also altered inflammatory responses at the protein and gene expression level. The concordance of transcriptional data in the mouse model and in patients with pneumococcal pneumonia supports the translational relevance of this work.
2024-06-05 | GSE246398 | GEO
Project description:Genomic epidemiology of the 2022-2023 cholera outbreak in Lebanon
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Project description:Pneumococcal meningitis outbreak in BAR Ghana 2016
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Project description:The goal of this study was to evaluate the impact of mechanical ventilation on immune and mitochondrial dysfunctions, in the setting of pneumococcal pneumonia in rabbits. Then, in a randomized trial, we assessed the effect of human umbilical cord-derived mesenchymal stem cells (MSCs), either alone, or in association with an atibiotic treatment (Ceftaroline) in the setting of pneumococcal pneumonia submitted to adverse mechanical ventilation. Pulmonary gene expression was analysed in an attempt to elucidate the effects of MSCs.
2021-04-24 | GSE173238 | GEO
Project description:Legionella pneumophila sg 1 outbreak connected to city water network, Finland 2021
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Project description:Outbreak of invasive pneumococcal disease connected to shipyard, Finland, May-October 2019
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Project description:Influenza A virus (IAV) predisposes individuals to secondary infections with the bacterium Streptococcus pneumoniae (the pneumococcus). Infections may manifest as pneumonia, sepsis, meningitis or otitis media (OM). It remains controversial as to whether secondary pneumococcal disease is due to the induction of an aberrant immune response or IAV induced immunosuppression. Moreover, as the majority of studies have been performed in the context of pneumococcal pneumonia, it remains unclear how far these findings can be extrapolated to other pneumococcal disease phenotypes. Here, we demonstrate that the viral hemagglutinin (HA) mediates bacterial OM by inducing a pro-inflammatory response in the middle ear cavity in a replication-dependent manner. Importantly, our findings show that it is the inflammatory response that mediates pneumococcal replication; not viral suppression of the immune system or epithelial damage. This study provide the first evidence that HA induced inflammation drives pneumococcal replication in the middle ear cavity, which has important consequences to the treatment of pneumococcal OM.
2013-01-01 | GSE41098 | GEO
Project description:IL-15 has critical impact on the homeostasis and activation of NK, NKT, gdT and CD8+T cells, and contributes to antimicrobial defenses particularly at mucosal sites. The respiratory tract also comprises a large mucosal surface and harbors significant amounts of lymphocytes, but the expression pattern of IL-15 in the lung and its role in local immune responses are largely unknown. We therefore analyzed the differential expression of IL-15 and the IL-15 receptor (IL-15R) complex in the lungs of mice, and demonstrated substantial constitutive expression in bronchial and alveolar epithelial cells, alveolar macrophages, and vascular smooth muscle cells, implicating contribution to pulmonary immune cell homeostasis already under normal conditions. The induction of pneumococcal pneumonia but not the infection with Chlamydophila pneumoniae evoked a significant up-regulation of IL-15 on alveolar macrophages and bronchial epithelial cells, with the latter presenting de-novo expression of IL-15 on their basolateral surface and additional up-regulation of IL-15Ra . Transcriptome analysis and semiquantitative PCR indicated at least partial transcriptional regulation. Finally, the increase of IL-15 was accompanied by enhanced expression of CD69, TNFa, IFNg and Bcl-2 by IL-15-dependent lymphocyte populations suggesting functional impact of IL-15 on the pulmonary immune response in pneumococcal pneumonia. Keywords: Streptococcus pneumoniae, pneumonia, IL-15
2006-03-01 | GSE3631 | GEO
Project description:Inflammasomes are multiprotein platforms of caspase-1 activation. The NLRP3 inflammasome is composed of NLRP3, ASC, and procaspase-1. This inflammasome is activated by various endogenous and exogenous stimuli, including pneumococci, and protects from a variety of microbial pathogens. In the present study, we examined the role of NLRP3 inflammasome components in gene expression in the lung during pneumococcal pneumina.
2014-12-31 | GSE56653 | GEO