Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology.
We show here that mouse interferon-alpha (IFN-alpha)-producing cells (mIPCs) are a unique subset of immature antigen-presenting cells (APCs) that secrete IFN-alpha upon stimulation with viruses. mIPCs have a plasmacytoid morphology, can be stained with an antibody to Ly6G and Ly6C (anti-Ly6G/C) and are Ly6C+B220+CD11cloCD4+; unlike other dendritic cell subsets, however, they do not express CD8alpha or CD11b. Although mIPCs undergo apoptosis in vitro, stimulation with viruses, IFN-alpha or CpG oligonucleotides enhanced their survival and T cell stimulatory activity. In vivo, mIPCs were the main producers of IFN-alpha in cytomegalovirus-infected mice, as depletion of Ly6G+/C+ cells abrogated IFN-alpha production. mIPCs produced interleukin 12 (IL-12) in response to viruses and CpG oligodeoxynucleotides, but not bacterial products. Although different pathogens can selectively engage various APC subsets for IL-12 production, IFN-alpha production is restricted to mIPCs' response to viral infection.
Asselin-Paturel
C
C
Schering-Plough, Laboratory for Immunological Research, Dardilly, France.
Boonstra
A
A
Dalod
M
M
Durand
I
I
Yessaad
N
N
Dezutter-Dambuyant
C
C
Vicari
A
A
O'Garra
A
A
Biron
C
C
Brière
F
F
Trinchieri
G
G
D000818:Animals; D000938:Antigen-Presenting Cells / Q000145:classification / Q000276:immunology* / Q000648:ultrastructure*; D001854:Bone Marrow Cells / Q000276:immunology; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D005260:Female; D006566:Herpesviridae Infections / Q000276:immunology; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000494:pharmacology; D018664:Interleukin-12 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018146:Muromegalovirus / Q000502:physiology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D009975:Orthomyxoviridae / Q000502:physiology; D013154:Spleen / Q000276:immunology
C408982:CPG-oligonucleotide; D016898:Interferon-alpha; D009838:Oligodeoxyribonucleotides; D018664:Interleukin-12