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

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Shabaani Namir, Duhan V, Khairnar V, Gassa A, Ferrer-Tur R, Häussinger D, Recher M, Zelinskyy G, Liu J, Dittmer U, Trilling M, Scheu S, Hardt C, Lang PA, Honke N, Lang KS,
Project Analysis of RAG-dependent immunodeficiency and autoimmunity
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Original article (peer-reviewed)

Journal Cell Death and Disease
Page(s) e2446
Title of proceedings Cell Death and Disease
DOI 10.1038/cddis.2016.350

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.
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