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

Platelets regulate human inflammatory responses that lead to disease. However, the role of platelets in tuberculosis (TB) pathogenesis is still unclear. Here, we show that patients with active TB have a high number of platelets in peripheral blood and a low number of lymphocytes leading to a high platelets to lymphocytes ratio (PL ratio). Moreover, the serum concentration of different mediators promoting platelet differentiation or associated with platelet activation is increased in active TB. Immunohistochemistry analysis shows that platelets localise around the lung granuloma lesions in close contact with T lymphocytes and macrophages. Transcriptomic analysis of caseous tissue of human pulmonary TB granulomas, followed by Gene Ontology analysis, shows that 53 platelet activation-associated genes are highly expressed compared to the normal lung tissue. In vitro activated platelets (or their supernatants) inhibit BCG-induced T- lymphocyte proliferation and IFN-gamma production. Likewise, platelets inhibit the growth of intracellular macrophages of Mycobacterium (M.) tuberculosis. Soluble factors released by activated platelets mediate both immunological and M. tuberculosis replication activities. Furthermore, proteomic and neutralisation studies (by mAbs) identify TGF-beta and PF4 as the factors responsible for inhibiting T-cell response and enhancing the mycobactericidal activity of macrophages, respectively. Altogether these results highlight the importance of platelets in TB pathogenesis.

Automated summary

Platelets play an important role in the pathogenesis of tuberculosis. Patients with active tuberculosis have higher platelet counts and lower lymphocyte counts, resulting in an elevated platelet to lymphocyte ratio. In addition, the concentration of platelet differentiation mediators and platelet activation-associated factors is increased in active tuberculosis. Immunohistochemistry analysis shows that platelets are located around lung granuloma lesions in close contact with T lymphocytes and macrophages. Transcriptomic analysis reveals that genes associated with platelet activation are highly expressed in caseous tissue of human pulmonary tuberculosis granulomas. In vitro studies demonstrate that activated platelets inhibit T lymphocyte proliferation and IFN-gamma production induced by BCG, as well as inhibit the growth of intracellular macrophages of Mycobacterium tuberculosis. The soluble factors released by activated platelets mediate both immunological and M. tuberculosis replication activities. TGF-beta and PF4 are identified as the factors responsible for inhibiting T-cell response and enhancing the mycobactericidal activity of macrophages, respectively. These findings highlight the importance of platelets in the pathogenesis of tuberculosis.