Submitted February 3, 2009
Accepted March 26, 2009
PD-1 on dendritic cells impedes innate immunity against bacterial infection
Sheng Yao, Shengdian Wang, Yuwen Zhu, Liqun Luo, Gefeng Zhu, Sarah Flies, Haiying Xu, William Ruff, Megan Broadwater, In-Hak Choi, Koji Tamada, and Lieping Chen*
Department of Oncology and Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States
Center for Infection and Immunity, Institute of Biophysics, Chinese Academy of Science, Beijing, China
Department of Microbiology, Inje University College of Medicine, Busan, Korea, Republic of
* Corresponding author; email: lchen42{at}jhmi.edu.
Programmed death one (PD-1) is an inducible molecule belonging to the immunoglobulin superfamily. It is expressed on activated T and B lymphocytes and plays pivotal roles in the negative regulation of adaptive immune responses. We report here an unexpected finding, that PD-1 could also be induced on splenic dendritic cells (DCs) by various inflammatory stimuli. Adoptive transfer of PD-1 deficient DCs demonstrates their superior capacity to wild type DCs in innate protection of mice against lethal infection by Listeria Monocytogenes. Furthermore, PD-1 deficient mice are also more resistant to the infection than wild type controls, even in the absence of T and B cells, accompanied by elevated production of DC-derived IL-12 and TNF-alpha. Our results reveal a novel role of PD-1 in the negative regulation of DC function during innate immune response.
