Project description:In August 2023, the Finnish Institute for Health and Welfare received reports of a potential cluster of pneumococcal pneumonia cases among shipyard employees in Turku, Finland. Considering a similar outbreak in the same shipyard in 2019, we initiated a case-control study to investigate individual and environmental risk factors specific to this occupational setting in order to inform targeted prevention measures. In total, 14 hospitalized cases were identified from 19 August to 15 October 2023. Streptococcus pneumoniae serotypes 4 and 9 V were isolated from blood cultures of seven cases. Eleven cases and 67 controls working at the shipyard were included in the case-control study. Compared with controls, cases were more likely to be living in an apartment/studio or a hotel/hostel, and less likely in a house or with family. Furthermore, cases were more likely to have a shorter duration of employment (< 1 year) at the shipyard compared to controls. Control measures, including an information and a vaccination campaign, were implemented. We emphasize shipyard-wide hygiene improvements and recommend nationwide consideration of expanding pneumococcal vaccination eligibility to all shipyard construction employees as an occupational high-risk group.
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.
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.
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.