Mycobacterium tuberculosis targets DC-SIGN for immunosuppression through the PD-1/PD-Ligand pathway
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ABSTRACT: The inhibitory axis of PD-1 expressed on T cells and its ligands produced by APCs mediates T cell exhaustion in chronic viral infection. We asked whether temporality of the infectious process is decisive for regulation through PD-1/PD-Ligand and investigated its impact on chronic bacterial infection. Here we show that M. tuberculosis and its lipid compounds induce expression of PD-Ligand on dendritic cells (DC). Upregulation of PD-Ligand depended on signaling through DC-SIGN upon infection. As a counterpart, expression of the PD-1 receptor was increased on T cells from tuberculosis patients and PPD+ donors compared to healthy normal individuals. Moreover, PD-1 expressing T cells were confined to granulomatous lesions in tuberculous lungs. Finally, functional blocking of PD-Ligand rescued antigen-specific T cell responses of tuberculosis patients. Taken together, we demonstrate that the inhibitory axis of PD-1/PD-Ligand is operative in mycobacterial infection and suggest inhibition of inhibition for rescuing exhausted T cells in tuberculosis. Keywords: Agilent two-color catolog 44K human whole genome microarrays
ORGANISM(S): Homo sapiens
PROVIDER: GSE10198 | GEO | 2008/02/01
SECONDARY ACCESSION(S): PRJNA108315
REPOSITORIES: GEO
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