期刊
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
卷 198, 期 2, 页码 245-255出版社
AMER THORACIC SOC
DOI: 10.1164/rccm.201710-2102OC
关键词
tuberculosis; matrix metalloproteinases; platelets; human; innate immunity
资金
- Wellcome Trust
- Imperial College National Institute for Health Research (NIHR) Biomedical Research Centre
- NIHR Academic Clinical Fellowship
- MRC Clinical Research Training Fellowships
- Medical Research Council New Investigator Research Grant
- University College London Hospitals NIHR Biomedical Research Centre
- Imperial College Trust
- charity Breathing Matters
- Medical Research Council [MR/K004158/1, MR/P019978/1, MR/P028225/1, MR/K007467/1, MR/P019978/2] Funding Source: researchfish
- MRC [MR/P019978/2, MR/P028225/1, MR/P019978/1, MR/K007467/1, MR/K004158/1] Funding Source: UKRI
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-1b concentrations. Conclusions: Platelets drive a proinflammatory, tissue-degrading phenotype in TB.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据