Platelets accumulate in lung lesions of tuberculosis patients and inhibit T‐cell responses and Mycobacterium tuberculosis replication in macrophages. Issue 5 (9th April 2022)

• Record Type: Journal Article
• Authors: La Manna, Marco P.; Orlando, Valentina; Badami, Giusto D.; Tamburini, Bartolo; Shekarkar Azgomi, Mojtaba; Lo Presti, Elena; del Nonno, Franca; Petrone, Linda; Belmonte, Beatrice; Falasca, Laura; Di Carlo, Paola; Dieli, Francesco; Goletti, Delia; Caccamo, Nadia
• Is Part Of: European journal of immunology. Volume 52:Issue 5(2022)
• Page Start: 784
• Page End: 799
• Publication Date: 2022-04-09
• Subjects: Cytokines -- Lymphocytes -- Macrophages -- Mycobacterium tuberculosis -- Platelets; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.202149549
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: 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‐γ 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‐β 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. Abstract : Platelets are important players in the immune response against Mycobacterium tuberculosis . They are present at the site of infection; they can downregulate the proliferation and cytokine production of T lymphocytes, and they may enhance the effector function of macrophages, decreasing mycobacterial replication.