Platelets Restrict the Oxidative Burst in Phagocytes and Facilitate Primary Progressive Tuberculosis
| Autor: | Dagmar Oberbeck-Müller, Hans-Joachim Mollenkopf, Joanna Zyla, Lisa Scheuermann, Anca Dorhoi, Silke Bandermann, Juan Sebastian Ruiz Moreno, Stefan H. E. Kaufmann, Yonghong Feng, Gang Pei, Teresa Domaszewska, Bastian Opitz |
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| Rok vydání: | 2020 |
| Předmět: |
Pulmonary and Respiratory Medicine
Blood Platelets Male Myeloid Tuberculosis T-Lymphocytes Critical Care and Intensive Care Medicine Mycobacterium tuberculosis 03 medical and health sciences Mice 0302 clinical medicine Immunopathology medicine Animals Platelet 030212 general & internal medicine Tuberculosis Pulmonary Respiratory Burst Phagocytes Innate immune system Lung biology business.industry biology.organism_classification medicine.disease Flow Cytometry Respiratory burst Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure 030228 respiratory system Immunology Disease Progression Female business |
| Zdroj: | American journal of respiratory and critical care medicine. 202(5) |
| ISSN: | 1535-4970 |
| Popis: | Rationale: Platelets are generated in the capillaries of the lung, control hemostasis, and display immunological functions. Tuberculosis primarily affects the lung, and patients show platelet changes and hemoptysis. A role of platelets in immunopathology of pulmonary tuberculosis requires careful assessment.Objectives: To identify the dynamics and interaction partners of platelets in the respiratory tissue and establish their impact on the outcome of pulmonary tuberculosis.Methods: Investigations were primarily performed in murine models of primary progressive pulmonary tuberculosis, by analysis of mouse strains with variable susceptibility to Mycobacterium tuberculosis infection using platelet depletion and delivery of antiplatelet drugs.Measurements and Main Results: Platelets were present at the site of infection and formed aggregates with different myeloid subsets during experimental tuberculosis. Such aggregates were also detected in patients with tuberculosis. Platelets were detrimental during the early phase of infection, and this effect was uncoupled from their canonical activation. Platelets left lung cell dynamics and patterns of antimycobacterial T-cell responses unchanged but hampered antimicrobial defense by restricting production of reactive oxygen species in lung-residing myeloid cells.Conclusions: Platelets are detrimental in primary progressive pulmonary tuberculosis, orchestrate lung immunity by modulating innate immune responsiveness, and may be amenable to new interventions for this deadly disease. |
| Databáze: | OpenAIRE |
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