Control of pathogenic effector T-cell activities in situ by PD-L1 expression on respiratory inflammatory dendritic cells during respiratory syncytial virus infection

Mucosal Immunol. 2015 Jul;8(4):746-59. doi: 10.1038/mi.2014.106. Epub 2014 Dec 3.


Respiratory syncytial virus (RSV) infection is a leading cause of severe lower respiratory tract illness in young infants, the elderly and immunocompromised individuals. We demonstrate here that the co-inhibitory molecule programmed cell death 1 (PD-1) is selectively upregulated on T cells within the respiratory tract during both murine and human RSV infection. Importantly, the interaction of PD-1 with its ligand PD-L1 is vital to restrict the pro-inflammatory activities of lung effector T cells in situ, thereby inhibiting the development of excessive pulmonary inflammation and injury during RSV infection. We further identify that PD-L1 expression on lung inflammatory dendritic cells is critical to suppress inflammatory T-cell activities, and an interferon-STAT1-IRF1 axis is responsible for increased PD-L1 expression on lung inflammatory dendritic cells. Our findings suggest a potentially critical role of PD-L1 and PD-1 interactions in the lung for controlling host inflammatory responses and disease progression in clinical RSV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Disease Models, Animal
  • Disease Progression
  • Gene Expression
  • Host-Pathogen Interactions
  • Humans
  • Interferon Regulatory Factor-1 / metabolism
  • Interferons / metabolism
  • Lymphocyte Activation / immunology
  • Mice
  • Programmed Cell Death 1 Receptor / metabolism
  • Respiratory Syncytial Virus Infections / genetics
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Infections / metabolism*
  • Respiratory Syncytial Virus Infections / pathology
  • Respiratory Syncytial Viruses / immunology*
  • STAT1 Transcription Factor / metabolism
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*


  • B7-H1 Antigen
  • Interferon Regulatory Factor-1
  • Programmed Cell Death 1 Receptor
  • STAT1 Transcription Factor
  • Interferons