IFN-beta-mediated up-regulation of CD1d in bacteria-infected APCs.
The expression of CD1d molecules is essential for the selection and activation of a unique subset of T cells, invariant NKT cells, which express limited TCR diversity and have been demonstrated to function in both regulatory and antimicrobial immune responses. Although it has been reported that the levels of CD1d expression can be modulated during infection, the mechanisms that mediate this effect are poorly defined. In this study, we show that infection of dendritic cells and macrophages both in vitro and in vivo with the intracellular pathogen Listeria monocytogenes leads to up-regulation of CD1d. IFN-beta is required to mediate this up-regulation in L. monocytogenes infection, as well as being sufficient to up-regulate CD1d expression in vitro. Unlike MHC class I molecules, the increased surface expression of CD1d by IFN-beta is not regulated at the transcriptional level. Confocal microscopy and metabolic labeling experiments show that the total pool of CD1d protein is increased in IFN-beta-treated cells and that increased surface expression of CD1d is not due to the redistribution of the intracellular pool of CD1d. IFN-beta treatment increases the de novo synthesis of CD1d. This change in surface CD1d expression was functionally relevant, as IFN-beta-treated dendritic cells are more efficient in stimulating invariant NKT cells than untreated controls. Taken together, these data support a role for early IFN-beta-mediated up-regulation of CD1d in NKT cell activation during infection.
Raghuraman
Gayatri
G
Department of Pathology, University of Chicago, 924 East 57th Street, Chicago, IL 60637, USA.
Geng
Yanbiao
Y
Wang
Chyung-Ru
CR
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000382:microbiology*; D018949:Antigens, CD1 / Q000096:biosynthesis*; D055610:Antigens, CD1d; D047468:Immunoprecipitation; D016899:Interferon-beta / Q000276:immunology / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology; D008088:Listeriosis / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D018949:Antigens, CD1; D055610:Antigens, CD1d; D016899:Interferon-beta