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  • 标题:PD-1/PD-L1 Pathway Modulates Macrophage Susceptibility to Mycobacterium tuberculosis Specific CD8+ T cell Induced Death
  • 本地全文:下载
  • 作者:Guadalupe Verónica Suarez ; Claudia del Carmen Melucci Ganzarain ; María Belén Vecchione
  • 期刊名称:Scientific Reports
  • 电子版ISSN:2045-2322
  • 出版年度:2019
  • 卷号:9
  • 期号:1
  • 页码:1-14
  • DOI:10.1038/s41598-018-36403-2
  • 出版社:Springer Nature
  • 摘要:CD8 + T cells contribute to tuberculosis (TB) infection control by inducing death of infected macrophages. Mycobacterium tuberculosis (Mtb) infection is associated with increased PD-1/PD-L1 expression and alternative activation of macrophages. We aimed to study the role of PD-1 pathway and macrophage polarization on Mtb-specific CD8 + T cell-induced macrophage death. We observed that both PD-L1 on CD14 + cells and PD-1 on CD8 + T cells were highly expressed at the site of infection in pleurisy TB patients' effusion samples (PEMC). Moreover, a significant increase in CD8 + T cells' Mtb-specific degranulation from TB-PEMC vs. TB-PBMC was observed, which correlated with PD-1 and PDL-1 expression. In an in vitro model, M1 macrophages were more susceptible to Mtb-specific CD8 + T cells' cytotoxicity compared to M2a macrophages and involved the transfer of cytolytic effector molecules from CD8 + T lymphocytes to target cells. Additionally, PD-L1 blocking significantly increased the in vitro Ag-specific CD8 + T cell cytotoxicity against IFN-γ-activated macrophages but had no effect over cytotoxicity on IL-4 or IL-10-activated macrophages. Interestingly, PD-L1 blocking enhanced Mtb-specific CD8 + T cell killing of CD14 + cells from human tuberculous pleural effusion samples. Our data indicate that PD-1/PD-L1 pathway modulates antigen-specific cytotoxicity against M1 targets in-vitro and encourage the exploration of checkpoint blockade as new adjuvant for TB therapies.
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