1. CD169+ macrophages regulate PD-L1 expression via type I interferon and thereby prevent severe immunopathology after LCMV infection
- Author
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Dieter Häussinger, Karl S. Lang, Mirko Trilling, Ulf Dittmer, Nadine Honke, Mike Recher, Gennadiy Zelinskyy, Vikas Duhan, Philipp A. Lang, Vishal Khairnar, Stefanie Scheu, A Gassa, Namir Shaabani, Jia Liu, Rita Ferrer-Tur, and Cornelia Hardt
- Subjects
0301 basic medicine ,Cancer Research ,Immunology ,Medizin ,Spleen ,Cell Biology ,Biology ,Lymphocytic choriomeningitis ,medicine.disease ,Virology ,Virus ,3. Good health ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,030104 developmental biology ,medicine.anatomical_structure ,Viral replication ,Interferon ,Immunopathology ,medicine ,Interferon type I ,CD8 ,medicine.drug - Abstract
Upon infection with persistence-prone virus, type I interferon (IFN-I) mediates antiviral activity and also upregulates the expression of programmed death ligand 1 (PD-L1), and this upregulation can lead to CD8+ T-cell exhaustion. How these very diverse functions are regulated remains unknown. This study, using the lymphocytic choriomeningitis virus, showed that a subset of CD169+ macrophages in murine spleen and lymph nodes produced high amounts of IFN-I upon infection. Absence of CD169+ macrophages led to insufficient production of IFN-I, lower antiviral activity and persistence of virus. Lack of CD169+ macrophages also limited the IFN-I-dependent expression of PD-L1. Enhanced viral replication in the absence of PD-L1 led to persistence of virus and prevented CD8+ T-cell exhaustion. As a consequence, mice exhibited severe immunopathology and died quickly after infection. Therefore, CD169+ macrophages are important contributors to the IFN-I response and thereby influence antiviral activity, CD8+ T-cell exhaustion and immunopathology.
- Published
- 2016