Platelet Activation and the Immune Response to Tuberculosis

Abstract

In 2019 10 million people developed symptomatic tuberculosis (TB) disease and 1.2 million died. In active TB the inflammatory response causes tissue destruction, which leads to both acute morbidity and mortality. Tissue destruction in TB is driven by host innate immunity and mediated via enzymes, chiefly matrix metalloproteinases (MMPs) which are secreted by leukocytes and stromal cells and degrade the extracellular matrix. Here we review the growing evidence implicating platelets in TB immunopathology. TB patients typically have high platelet counts, which correlate with disease severity, and a hypercoagulable profile. Platelets are present in human TB granulomas and platelet-associated gene transcripts are increased in TB patients versus healthy controls. Platelets most likely drive TB immunopathology through their effect on other immune cells, particularly monocytes, to lead to upregulation of activation markers, increased MMP secretion, and enhanced phagocytosis. Finally, we consider current evidence supporting use of targeted anti-platelet agents in the treatment of TB due to growing interest in developing host-directed therapies to limit tissue damage and improve treatment outcomes. In summary, platelets are implicated in TB disease and contribute to MMP-mediated tissue damage via their cellular interactions with other leukocytes, and are potential targets for novel host-directed therapies.

Platelets accumulate in lung lesions of tuberculosis patients and inhibit T‐cell responses and Mycobacterium tuberculosis replication in macrophages

“…We found that TGF-β and PF4 are representative protein signatures, confirming the result of the transcriptomic analysis and allowing us to hypothesize for these two molecules a potential role as mediators of the modulatory effects by activated platelets in vitro [21].…”

“…Blood was collected in EDTA tubes centrifuged at 120 × g for 10 min at room temperature to prepare platelet‐rich plasma (PRP). The erythrocyte‐ and leukocyte‐free PRP was collected and transferred in another tube without anticoagulant for second centrifugation at 800 × g for a further 5 min [21]. Finally, the serum component was removed, and the platelets were resuspended in 2 mL of PBS 1×, pH 7.4 and used for further experiments.…”

Neutrophil-Mediated Immunopathology and Matrix Metalloproteinases in Central Nervous System – Tuberculosis

“…Hydrocephalus, which is the most frequent cause of raised intracranial pressure in TBM patients, was also found to be associated with advanced stage of infection, with high morbidity and mortality (18,57). Cerebral vasculitis and inflammation both of which are regulated by platelet activation result in infarcts and are the primary cause of permanent brain tissue damage in TBM (58)(59)(60).…”

“…These findings also indicated a hypercoagulable state in TBM which is more pronounced in stage III of TBM with increased risk of thrombosis and infarction ( 207 ). Platelets are likely to be key in the inflammatory and thrombotic response to CNS-TB ( 60 ).…”

Pulmonary Tuberculosis-Related Ischemic Stroke: A Retrospective Case Control Study

“…When pulmonary tuberculosis is active, elevated plasma inflammatory factors, such as C-reactive protein, increased platelet activation and the development of a hypercoagulable state, may be continued. [12][13][14] More importantly, elevated plasma inflammatory factors, such as C-reactive protein, platelet activation and the hypercoagulable state, have been found to contribute not only to an increased risk of ischemic stroke but also to a poor prognosis. [15][16][17][18] As a result, it was hypothesized that active pulmonary tuberculosis may lead to ischemic stroke through elevated plasma inflammatory factors, such as C-reactive protein, platelet activation and/or hypercoagulability, namely TBRIS.…”