A recent study found that markers of platelet activity are increased in plasma of patients with pulmonary tuberculosis and these are then normalized with antimycobacterial treatment. The researchers said their findings could have implications for new types of drug therapies.
A recent study found that markers of platelet activity are increased in the plasma of patients with pulmonary tuberculosis (TB), and these are then normalized with antimycobacterial treatment.
The researchers said their data could have implications for “host-directed therapies in the era of increasing drug resistance.” The study was published in a recent issue of the American Journal of Respiratory and Critical Care Medicine.
In TB, inflammatory tissue damage leads to cavity formation and transmission, morbidity, and mortality. Approximately 2 billion people are infected with Mycobacterium tuberculosis (M tuberculosis), which killed close to 2 million people in 2015.
In addition to their role in coagulation, platelets have a role in immune responses, but it is unknown as to how they work in cellular networks of inflammatory tissue destruction in TB.
Platelet interaction with monocytes regulates cell recruitment, maturation, and secretion of cytokines and matrix metalloproteinases (MMPs). High platelet numbers are found in pulmonary vessels, and the lung is a major site of platelet production.
In this study, researchers examined plasma from 50 patients with TB, before treatment, and 50 control subjects for markers of platelet activation. Twenty-five patients were followed longitudinally.
Platelet—monocyte interactions were studied in a coculture model infected with live, virulent M tuberculosis and dissected using real-time quantitative reverse transcription polymerase chain reaction, 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.
Five of 6 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 tuberculosis infection. Platelets also enhanced M tuberculosis—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 tuberculosis 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.
Fox KA, Kirwan DE, Whittington AM, et al. Platelets regulate inflammation in tuberculosis. Am J Respir Crit Care Med. 2018;198(2):245-255. doi: 10.1164/rccm.201710-2102OC.