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The Journal of Immunology, 2005, 175: 421-432.
Copyright © 2005 by The American Association of Immunologists

Listeria-Infected Myeloid Dendritic Cells Produce IFN-{beta}, Priming T Cell Activation 1

Hanping Feng2,*,{dagger}, Dong Zhang*,{dagger}, Deborah Palliser*,{dagger}, Pengcheng Zhu*,{dagger}, Shenghe Cai*, Ann Schlesinger*,{dagger}, Laura Maliszewski* and Judy Lieberman3,*,{dagger}

* CBR Institute for Biomedical Research and {dagger} Department of Pediatrics, Harvard Medical School, Boston, MA 02115

The intracellular bacterium Listeria monocytogenes infects dendritic cells (DC) and other APCs and induces potent cell-mediated protective immunity. However, heat-killed bacteria fail to do so. This study explored whether DC differentially respond to live and killed Listeria and how this affects T cell activation. To control for bacterial number, a replication-deficient strain, Lmdd, defective in D-alanine biosynthesis, was used. We found that DC internalize both live and heat-killed Lmdd and similarly up-regulate the expression of costimulatory molecules, a necessary step for T cell activation. However, only live Lmdd-infected DC stimulate T cells to express the early activation marker CD69 and enhance T cell activation upon TCR engagement. Infection with live, but not heat-killed, Lmdd induces myeloid DC to secrete copious amounts of IFN-{beta}, which requires bacterial cytosolic invasion. Exposure to high concentrations of IFN-{beta} sensitizes naive T cells for Ag-dependent activation.




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