CD169+macrophages regulate PD-L1 expression via type I interferon and thereby prevent severe immunopathology after LCMV infection.
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.
Institute of Immunology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.|Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.|Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.
Namir
N
Shaabani
Institute of Immunology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Vikas
V
Duhan
Institute of Immunology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Vishal
V
Khairnar
Institute of Immunology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Asmae
A
Gassa
Institute of Immunology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Rita
R
Ferrer-Tur
Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
Dieter
D
Häussinger
Clinic for Primary Immunodeficiency, Medical Outpatient Unit and Immunodeficiency Laboratory, Department of Biomedicine, University Hospital, Basel, Switzerland.
Mike
M
Recher
Institute of Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Gennadiy
G
Zelinskyy
Department of Infectious Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Jia
J
Liu
Institute of Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Ulf
U
Dittmer
Institute of Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Mirko
M
Trilling
Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
Stefanie
S
Scheu
Institute of Immunology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Cornelia
C
Hardt
Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
Philipp A
PA
Lang
Institute of Immunology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.|Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
Nadine
N
Honke
Institute of Immunology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.|Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
Karl S
KS
Lang
D000818:Animals; D060890:B7-H1 Antigen / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002908:Chronic Disease; D045142:Cross-Priming / Q000276:immunology; D007370:Interferon Type I / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008198:Lymph Nodes / Q000378:metabolism; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D063267:Sialic Acid Binding Ig-like Lectin 1 / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism
D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D007370:Interferon Type I; D063267:Sialic Acid Binding Ig-like Lectin 1