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-Mediated Up-Regulation of CD1d in Bacteria-Infected APCs1
Department of Pathology, University of Chicago, Chicago, IL 60637
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-
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- 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--treated cells and that increased surface expression of CD1d is not due to the redistribution of the intracellular pool of CD1d. IFN- treatment increases the de novo synthesis of CD1d. This change in surface CD1d expression was functionally relevant, as IFN--treated dendritic cells are more efficient in stimulating invariant NKT cells than untreated controls. Taken together, these data support a role for early IFN--mediated up-regulation of CD1d in NKT cell activation during infection.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grant R01 AI43407 (to C.-R.W.).
2 Address correspondence and reprint requests to Dr. Chyung-Ru Wang, Department of Pathology, University of Chicago, 924 East 57th Street, Biological Sciences Learning Center, Room 116, Chicago, IL 60637-5420. E-mail address: cwang{at}uchicago.edu
3 Abbreviations used in this paper: DC, dendritic cell; 2m, 2-microglobulin; iNKT, invariant NKT; 
-GalCer, -galactosylceramide; LM, Listeria monocytogenes; WT, wild type; BMDC, bone marrow-derived DC; HKLM, heat-killed LM; ISGF3, IFN-stimulated gene factor 3; KO, knockout; LM-CM, conditioned medium from LM-infected DC.
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