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Search: WFRF:(Schaible Ulrich E)

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  • Corleis, Björn, et al. (author)
  • Escape of Mycobacterium tuberculosis from oxidative killing by neutrophils.
  • 2012
  • In: Cellular microbiology. - : Hindawi Limited. - 1462-5822 .- 1462-5814. ; 14:7, s. 1109-1121
  • Journal article (peer-reviewed)abstract
    • Neutrophils enter sites of infection, where they can eliminate pathogenic bacteria in an oxidative manner. Despite their predominance in active tuberculosis lesions, the function of neutrophils in this important human infection is still highly controversial. We observed that virulent Mycobacterium tuberculosis survived inside human neutrophils despite prompt activation of these defence cells' microbicidal effectors. Survival of M.tuberculosis was accompanied by necrotic cell death of infected neutrophils. Necrotic cell death entirely depended on radical oxygen species production since chronic granulomatous disease neutrophils were protected from M.tuberculosis-triggered necrosis. More, importantly, the M. tuberculosisΔRD1 mutant failed to induce neutrophil necrosis rendering this strain susceptible to radical oxygen species-mediated killing. We conclude that this virulence function is instrumental for M.tuberculosis to escape killing by neutrophils and contributes to pathogenesis in tuberculosis.
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3.
  • Kontsevaya, Irina, et al. (author)
  • Perspectives for systems biology in the management of tuberculosis
  • 2021
  • In: European Respiratory Review. - : European Respiratory Society (ERS). - 0905-9180 .- 1600-0617. ; 30:160
  • Research review (peer-reviewed)abstract
    • Standardised management of tuberculosis may soon be replaced by individualised, precision medicine-guided therapies informed with knowledge provided by the field of systems biology. Systems biology is a rapidly expanding field of computational and mathematical analysis and modelling of complex biological systems that can provide insights into mechanisms underlying tuberculosis, identify novel biomarkers, and help to optimise prevention, diagnosis and treatment of disease. These advances are critically important in the context of the evolving epidemic of drug-resistant tuberculosis. Here, we review the available evidence on the role of systems biology approaches - human and mycobacterial genomics and transcriptomics, proteomics, lipidomics/metabolomics, immunophenotyping, systems pharmacology and gut microbiomes - in the management of tuberculosis including prediction of risk for disease progression, severity of mycobacterial virulence and drug resistance, adverse events, comorbidities, response to therapy and treatment outcomes. Application of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach demonstrated that at present most of the studies provide "very low" certainty of evidence for answering clinically relevant questions. Further studies in large prospective cohorts of patients, including randomised clinical trials, are necessary to assess the applicability of the findings in tuberculosis prevention and more efficient clinical management of patients.
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