1,721,545 research outputs found
Correction: Increased von willebrand factor, decreased ADAMTS13 and thrombocytopenia in melioidosis (PLoS Negl Trop Dis 11(3), e0005468, 10.1371/journal.pntd.0005468 PMID: 28296884)
No full textThere is an error in the article XML causing the eighth author’s name to be indexed incorrectly. The name should be indexed as van der Poll T
219-CC8893-VanderSluijs.indd
No full textBench-to-bedside review: Bacterial pneumonia with influenza -pathogenesis and clinical implications van der Sluijs, K.F.; van der Poll, T.; Lutter, R.; Juffermans, N.P.; Schultz, M.J
Sepsis in HIV-infected patients; epidemiology and host response
Get PDFIn this thesis, we examined the impact of HIV infection on the epidemiology (Part I) of sepsis, and host response (Part II) to sepsis. We studied sepsis patients in Gabon, a setting with a high prevalence of HIV, and in Dutch intensive care units (ICUs). In Part I, we found that HIV positive patients are more likely to present with bacterial sepsis, compared to HIV negative patients, in particular with pathogens like non-typhoid Salmonella and Streptococcus pneumoniae. Although sepsis patients with HIV co-infection in Gabon had increased mortality, HIV patients admitted to the ICU with sepsis in the Netherlands no longer had a survival disadvantage compared to HIV negative patients with sepsis. In Part II, we examined multiple components of the immune system, including neutrophil extracellular traps, cytokine release, coagulation, the complement system and the genomic response to sepsis. Differences in the host response to sepsis according to HIV status were most profound in our cohort in Gabon, while we found little impact of HIV co-infection on the host response to sepsis in Dutch ICU patients. Although HIV is well known for its immunosuppressive effect, we found no evidence for HIV induced suppression of the pro-inflammatory response. In contrast, our findings support the idea of HIV as a cause of chronic inflammation, which may result in a more profound inflammatory response and increased collateral damage during sepsis. Therefore, immune-modulatory treatment strategies may be of particular benefit to sepsis patients with HIV, which is an interesting area for further research
Modulation of innate immunity during endotoxemia and gram-negative infection
Get PDFLower respiratory tract infection is the fourth most common cause of death in the world. Pneumonia can result in sepsis, which is a major cause or morbidity and mortality worldwide. The research described in this thesis focuses on the innate immune response during gram-negative (bacterial) infection, particularly pneumonia and sepsis. For this we made use of established human (endotoxemia) and mouse models (bacterial pneumonia and sepsis).We first studied the role of mesenchymal stem cells (MSCs) as potential new sepsis therapy. We used adipose-derived mesenchymal stem cells (ASCs) in a randomized placebo controlled endotoxemia trial. We found that ASC infusion was well tolerated and resulted in mixed proinflammatory and anti-inflammatory responses. In addition, ASC infusion resulted in a transient systemic procoagulant effect. In a murine model of Klebsiella pneumoniae derived pneumosepsis, we show that treatment with human ASCs resulted in immune modulatory effects in the lung, associated with less bacterial outgrowth and reduced lung inflammation. We furthermore found that ASCs express tissue factor dependent procoagulant activity.To gain more knowledge on the pathophysiology we studied two important mediatiors of innate immunity, MMP-8 and caspase-11. Using MMP-8 and caspase-11 knock-out mice respectively, we were able to show their effects in a murine model of pneumosepsis. We show a limited role for MMP-8 in the host response. Caspase-11 deficiency was associated with less fibrin formation and more bacterial outgrowth in the lungs
Epigenetic regulation in epithelial and myeloid cells during lung infection and fibrosis
Get PDFEpithelial cells line the surface of the respiratory system and maintain homeostasis under normal conditions and play an eminent role in the initiation of immune responses during lung diseases, including the two pulmonary disorders studied in this thesis: infection and fibrosis. Together with immune cells, epithelial cells orchestrate the early local response to pathogens and non-infectious danger signals, and this complex reaction is regulated at different levels. Epigenetic regulation is one of the mechanisms that control epithelial and myeloid cell responses. DNA methylation is one of the most intensively studied epigenetic modifications. DNA methylation is established and maintained by DNA methyltransferases including Dnmt1, Dnmt3a and Dnmt3b, while methylation is removed by Tet methylcytosine dioxygenase family proteins (Tets). This thesis focused on the role of DNA methylation and the DNA methylation modifiers Dnmt3b and Tet2 in respiratory epithelial cells and myeloid cells during lung infection and fibrosis. We have done so by generating mice with epithelial or myeloid cell specific deficiency of Dnmt3b and Tet2, and by using well-established models of (a) bacterial pneumonia induced by infection with viable Pseudomonas aeruginosa or Klebsiella pneumoniae, important causative pathogens in hospital-acquired pneumonia, via the airways, (b) lung inflammation induced by local instillation of the bacterial components flagellin (expressed by Pseudomonas) or lipopolysaccharide (expressed by both Pseudomonas and Klebsiella), and (c) lung fibrosis induced by local of bleomycin. In one Chapter we in addition utilized a murine model of bacterial peritonitis and sepsis, using intraperitoneal infection with Escherichia coli
- …
