Platelets Regulate Pulmonary Inflammation and Tissue Destruction in Tuberculosis
| Autor: | Nitya Krishnan, José W. López, Katharine Fox, Ashley M. Whittington, Daniela E. Kirwan, Shivani Singh, Robert H. Gilman, Joanna C. Porter, Jon S. Friedland, Brian D. Robertson |
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| Přispěvatelé: | Imperial College Trust, Medical Research Council (MRC) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Respiratory System Apoptosis Matrix metalloproteinase Critical Care and Intensive Care Medicine ACTIVATION INFECTION INTERLEUKIN-1 Platelet innate immunity 11 Medical and Health Sciences biology INDUCTION Interleukin matrix metalloproteinases medicine.anatomical_structure DIFFERENTIATION tuberculosis platelets Female MYCOBACTERIUM-TUBERCULOSIS purl.org/pe-repo/ocde/ford#3.02.08 [https] Life Sciences & Biomedicine Pulmonary and Respiratory Medicine Platelets Adult Blood Platelets Tuberculosis IMMUNE Mycobacterium tuberculosis 03 medical and health sciences Immune system Critical Care Medicine General & Internal Medicine medicine Humans human Cell Proliferation Innate immune system Lung Science & Technology business.industry Original Articles Pneumonia medicine.disease biology.organism_classification 030104 developmental biology purl.org/pe-repo/ocde/ford#3.02.07 [https] Immunology business LUNG |
| ISSN: | 1535-4970 |
| Popis: | RATIONALE: Platelets may interact with the immune system in tuberculosis (TB) to regulate human inflammatory responses that lead to morbidity and spread of infection. OBJECTIVES: To identify a functional role of platelets in the innate inflammatory and matrix-degrading response in TB. METHODS: Markers of platelet activation were examined in plasma from 50 patients with TB before treatment and 50 control subjects. Twenty-five patients were followed longitudinally. Platelet-monocyte interactions were studied in a coculture model infected with live, virulent Mycobacterium tuberculosis (M.tb) and dissected using qRT-PCR, Luminex multiplex arrays, matrix degradation assays, and colony counts. Immunohistochemistry detected CD41 (cluster of differentiation 41) expression in a pulmonary TB murine model, and secreted platelet factors were measured in BAL fluid from 15 patients with TB and matched control subjects. MEASUREMENTS AND MAIN RESULTS: Five of six platelet-associated mediators were upregulated in plasma of patients with TB compared with control subjects, with concentrations returning to baseline by Day 60 of treatment. Gene expression of the monocyte collagenase MMP-1 (matrix metalloproteinase-1) was upregulated by platelets in M.tb infection. Platelets also enhanced M.tb-induced MMP-1 and -10 secretion, which drove type I collagen degradation. Platelets increased monocyte IL-1 and IL-10 and decreased IL-12 and MDC (monocyte-derived chemokine; also known as CCL-22) secretion, as consistent with an M2 monocyte phenotype. Monocyte killing of intracellular M.tb was decreased. In the lung, platelets were detected in a TB mouse model, and secreted platelet mediators were upregulated in human BAL fluid and correlated with MMP and IL-1β concentrations. CONCLUSIONS: Platelets drive a proinflammatory, tissue-degrading phenotype in TB. |
| Databáze: | OpenAIRE |
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