Listeria-infected myeloid dendritic cells produce IFN-beta, priming T cell activation.
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.
CBR Institute for Biomedical Research and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Hanping
H
Feng
Dong
D
Zhang
Deborah
D
Palliser
Pengcheng
P
Zhu
Shenghe
S
Cai
Ann
A
Schlesinger
Laura
L
Maliszewski
Judy
J
Lieberman
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D006358:Hot Temperature; D066298:In Vitro Techniques; D016899:Interferon-beta / Q000096:biosynthesis* / Q000235:genetics; D037181:Lectins, C-Type; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D022423:Myeloid Cells / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D016899:Interferon-beta; D037181:Lectins, C-Type; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D000099192:CD69 Antigens; C485468:Cd3e protein, mouse