Platelets accumulate in lung lesions of tuberculosis patients and inhibit T-cell responses and Mycobacterium tuberculosis replication in macrophages
© 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:52 |
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| Enthalten in: |
European journal of immunology - 52(2022), 5 vom: 09. Mai, Seite 784-799 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
La Manna, Marco P [VerfasserIn] |
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| Links: |
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| Themen: |
Cytokines |
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| Anmerkungen: |
Date Completed 10.05.2022 Date Revised 31.07.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/eji.202149549 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a © 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Cytokines | |
| 650 | 4 | |a Lymphocytes | |
| 650 | 4 | |a Macrophages | |
| 650 | 4 | |a Mycobacterium tuberculosis | |
| 650 | 4 | |a Platelets | |
| 700 | 1 | |a Orlando, Valentina |e verfasserin |4 aut | |
| 700 | 1 | |a Badami, Giusto D |e verfasserin |4 aut | |
| 700 | 1 | |a Tamburini, Bartolo |e verfasserin |4 aut | |
| 700 | 1 | |a Shekarkar Azgomi, Mojtaba |e verfasserin |4 aut | |
| 700 | 1 | |a Lo Presti, Elena |e verfasserin |4 aut | |
| 700 | 1 | |a Del Nonno, Franca |e verfasserin |4 aut | |
| 700 | 1 | |a Petrone, Linda |e verfasserin |4 aut | |
| 700 | 1 | |a Belmonte, Beatrice |e verfasserin |4 aut | |
| 700 | 1 | |a Falasca, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Di Carlo, Paola |e verfasserin |4 aut | |
| 700 | 1 | |a Dieli, Francesco |e verfasserin |4 aut | |
| 700 | 1 | |a Goletti, Delia |e verfasserin |4 aut | |
| 700 | 1 | |a Caccamo, Nadia |e verfasserin |4 aut | |
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