Immunology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
PLoS One. 2011 May 12;6(5):e19864. doi: 10.1371/journal.pone.0019864.
Programmed Death-1 (PD-1; CD279) receptor molecule is widely believed to be a negative regulator predominantly expressed by exhausted/activated mouse T cells. Upon interaction with its ligands, PD-L1 and PD-L2, PD-1 inhibits activation of T cells and cytokine production, which has been documented in various viral and fungal infections as well as in vitro studies. Therefore, inhibition of T cell responses by PD-1 resulted in disease resistance in a variety of mouse infection models studied heretofore.
METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that PD-1 deficient (PD-1(-/-)) mice infected with Mycobacterium tuberculosis (M. tb) H37Rv by the aerosol route have increased susceptibility as compared with their wild type littermates. Surprisingly, M. tb antigen-specific T cell proliferation was dramatically reduced in PD-1 deficient animals compared with wild-type littermates, and this was due to increased numbers of regulatory T cells (Tregs) and recruitment of mesenchymal stem cells. Furthermore, PD-1(-/-) mice exhibited decreases in the autophagy-induced LC3-B marker protein in macrophages.
CONCLUSIONS/SIGNIFICANCE: Our findings suggest that PD-1 does not play an inhibitory role during M. tb infection and instead promotes mycobacterial clearance in mice.
程序性死亡受体-1（PD-1；CD279）受体分子被广泛认为是一种主要表达在耗尽/激活的小鼠 T 细胞上的负调节剂。在与配体 PD-L1 和 PD-L2 相互作用后，PD-1 抑制 T 细胞的激活和细胞因子的产生，这在各种病毒和真菌感染以及体外研究中都有记录。因此，PD-1 抑制 T 细胞反应导致迄今为止研究的各种小鼠感染模型中的疾病抵抗力增强。
方法/主要发现：在这里，我们报告说，与野生型同窝仔相比，经气溶胶途径感染结核分枝杆菌（M. tb）H37Rv 的 PD-1 缺陷（PD-1(-/-)) 小鼠易感性增加。令人惊讶的是，与野生型同窝仔相比，PD-1 缺陷动物中的 M. tb 抗原特异性 T 细胞增殖显著减少，这是由于调节性 T 细胞（Tregs）数量增加和间充质干细胞的募集。此外，PD-1(-/-) 小鼠中巨噬细胞中的自噬诱导 LC3-B 标记蛋白减少。
结论/意义：我们的发现表明，PD-1 在 M. tb 感染过程中不发挥抑制作用，反而促进小鼠中分枝杆菌的清除。
