Imperial College London
Alternate

DrBrianRobertson

Faculty of Medicine, Department of Infectious Disease

Reader in Systems Microbiology
 
 
 
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Contact

 

b.robertson

 
 
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Location

 

3.41Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Fox:2018:10.1164/rccm.201710-2102OC,
author = {Fox, KA and Kirwan, DE and Whittington, AM and Krishnan, N and Robertson, BD and Gilman, RH and López, JW and Singh, S and Porter, JC and Friedland, JS},
doi = {10.1164/rccm.201710-2102OC},
journal = {American Journal of Respiratory and Critical Care Medicine},
pages = {245--255},
title = {Platelets regulate pulmonary inflammation and tissue destruction in tuberculosis},
url = {http://dx.doi.org/10.1164/rccm.201710-2102OC},
volume = {198},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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 TB patients pre-treatment, and 50 controls. 25 patients were followed longitudinally. Platelet-monocyte interactions were studied in a co-culture model infected with live, virulent Mycobacterium tuberculosis (M.tb) and dissected using qPCR, Luminex multiplex arrays, matrix degradation assays and colony counts. Immunohistochemistry detected CD41 expression in a pulmonary TB murine model and secreted platelet factors were measured in bronchoalveolar lavage fluid (BALF) from 15 TB patients and matched controls. MEASUREMENTS AND MAIN RESULTS: Five of six platelet-associated mediators were upregulated in plasma of TB patients compared to controls, with concentrations returning to baseline by day 60 of treatment. Gene expression of the monocyte collagenase MMP-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 monocyte-derived chemokine (MDC, 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 BALF, and correlated with MMP and IL-1β concentrations. CONCLUSIONS: Platelets drive a pro-inflammatory, tissue-degrading phenotype in TB.
AU  - Fox,KA
AU  - Kirwan,DE
AU  - Whittington,AM
AU  - Krishnan,N
AU  - Robertson,BD
AU  - Gilman,RH
AU  - López,JW
AU  - Singh,S
AU  - Porter,JC
AU  - Friedland,JS
DO  - 10.1164/rccm.201710-2102OC
EP  - 255
PY  - 2018///
SN  - 1073-449X
SP  - 245
TI  - Platelets regulate pulmonary inflammation and tissue destruction in tuberculosis
T2  - American Journal of Respiratory and Critical Care Medicine
UR  - http://dx.doi.org/10.1164/rccm.201710-2102OC
UR  - http://hdl.handle.net/10044/1/57077
VL  - 198
ER  -
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