Journal Article

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

Recher, Mike, Ferrer-Tur, Rita, Haeussinger, Dieter, Scheu, Stefanie, Dittmer, Ulf, Trilling, Mirko, Duhan, Vikas, Lang, Philipp A, Khairnar, Vishal, Gassa, Asmae, Zelinskyy, Gennadiy, Honke, Nadine, Hardt, Cornelia, Lang, Karl S, Shaabani, Namir, Liu, Jia

2016

Overview

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 super(+) 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 super(+) macrophages in murine spleen and lymph nodes produced high amounts of IFN-I upon infection. Absence of CD169 super(+) macrophages led to insufficient production of IFN-I, lower antiviral activity and persistence of virus. Lack of CD169 super(+) 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 super(+) T-cell exhaustion. As a consequence, mice exhibited severe immunopathology and died quickly after infection. Therefore, CD169 super(+) macrophages are important contributors to the IFN-I response and thereby influence antiviral activity, CD8 super(+) T-cell exhaustion and immunopathology.

• Subject: Arenaviridae