QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, Queensland 4006, Australia.
The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, Victoria 3000, Australia.
Nat Rev Immunol. 2018 Feb;18(2):91-104. doi: 10.1038/nri.2017.112. Epub 2017 Oct 9.
The upregulation of immune checkpoint molecules, such as programmed cell death protein 1 (PD1) and cytotoxic T lymphocyte antigen 4 (CTLA4), on immune cells occurs during acute infections, such as malaria, as well as during chronic persistent viral infections, including HIV and hepatitis B virus. These pathways are important for preventing immune-driven pathology but can also limit immune-mediated clearance of the infection. The recent success of immune checkpoint blockade in cancer therapy suggests that targeting these pathways would also be effective for preventing and treating a range of infectious diseases. Here, we review our current understanding of immune checkpoint pathways in the pathogenesis of infectious diseases and discuss the potential for therapeutically targeting these pathways in this setting.
免疫细胞表面的免疫检查点分子(如程序性细胞死亡蛋白 1(PD1)和细胞毒性 T 淋巴细胞抗原 4(CTLA4))的上调发生在急性感染(如疟疾)以及慢性持续性病毒感染(包括 HIV 和乙型肝炎病毒)期间。这些途径对于防止免疫驱动的病理很重要,但也会限制感染的免疫介导清除。免疫检查点阻断在癌症治疗中的近期成功表明,针对这些途径也将有效预防和治疗一系列传染病。在这里,我们回顾了我们目前对传染病发病机制中免疫检查点途径的理解,并讨论了在这种情况下靶向这些途径的治疗潜力。