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Platelets Regulate Pulmonary Inflammation and Tissue Destruction in Tuberculosis

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dc.contributor.author Fox, Katharine A.
dc.contributor.author Kirwan, Daniela E.
dc.contributor.author Whittington, Ashley M.
dc.contributor.author Krishnan, Nitya
dc.contributor.author Robertson, Brian D.
dc.contributor.author Gilman, Robert H.
dc.contributor.author López, José W.
dc.contributor.author Singh, Shivani
dc.contributor.author Porter, Joanna C.
dc.contributor.author Friedland, Jon S.
dc.date.accessioned 2018-11-30T22:50:35Z
dc.date.available 2018-11-30T22:50:35Z
dc.date.issued 2018
dc.identifier.uri https://hdl.handle.net/20.500.12866/4152
dc.description.abstract 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. en_US
dc.language.iso eng
dc.publisher American Thoracic Society
dc.relation.ispartof urn:issn:1535-4970
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject tuberculosis en_US
dc.subject human en_US
dc.subject innate immunity en_US
dc.subject matrix metalloproteinases en_US
dc.subject platelets en_US
dc.title Platelets Regulate Pulmonary Inflammation and Tissue Destruction in Tuberculosis en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1164/rccm.201710-2102OC
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.00 es_PE
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.07
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.08


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