CD169+ macrophages regulate PD-L1 expression via type I interferon and thereby prevent severe immunopathology after LCMV infection.

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.

• Authors: Namir Shaabani, Vikas Duhan, Vishal Khairnar, Asmae Gassa, Rita Ferrer-Tur, Dieter Häussinger, Mike Recher, Gennadiy Zelinskyy, Jia Liu, Ulf Dittmer, Mirko Trilling, Stefanie Scheu, Cornelia Hardt, Philipp A Lang, Nadine Honke, Karl S Lang
• Journal: Cell death & disease (Cell Death Dis) Vol. 7 Issue 11 Pg. e2446 (11 03 2016) ISSN: 2041-4889 [Electronic] England
• PMID: 27809306 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• B7-H1 Antigen
• Cd274 protein, mouse
• Interferon Type I
• Sialic Acid Binding Ig-like Lectin 1

Topics

• Animals
• B7-H1 Antigen (metabolism)
• CD8-Positive T-Lymphocytes (metabolism)
• Chronic Disease
• Cross-Priming (immunology)
• Interferon Type I (metabolism)
• Liver (metabolism, pathology, virology)
• Lymph Nodes (metabolism)
• Lymphocytic Choriomeningitis (immunology, pathology, virology)
• Lymphocytic choriomeningitis virus (physiology)
• Macrophages (metabolism)
• Mice, Inbred C57BL
• Sialic Acid Binding Ig-like Lectin 1 (metabolism)
• Spleen (metabolism)