Interleukin 12p40 is required for dendritic cell migration and T cell priming after Mycobacterium tuberculosis infection.
Migration of dendritic cells (DCs) to the draining lymph node (DLN) is required for the activation of naive T cells. We show here that migration of DCs from the lung to the DLN after Mycobacterium tuberculosis (Mtb) exposure is defective in mice lacking interleukin (IL)-12p40. This defect compromises the ability of IL-12p40-deficient DCs to activate naive T cells in vivo; however, DCs that express IL-12p40 alone can activate naive T cells. Treatment of IL-12p40-deficient DCs with IL-12p40 homodimer (IL-12(p40)(2)) restores Mtb-induced DC migration and the ability of IL-12p40-deficient DCs to activate naive T cells. These data define a novel and fundamental role for IL-12p40 in the pathogen-induced activation of pulmonary DCs.
Khader
Shabaana A
SA
Trudeau Institute, Inc., Saranac Lake, NY 12983, USA.
Partida-Sanchez
Santiago
S
Bell
Guy
G
Jelley-Gibbs
Dawn M
DM
Swain
Susan
S
Pearl
John E
JE
Ghilardi
Nico
N
Desauvage
Frederic J
FJ
Lund
Frances E
FE
Cooper
Andrea M
AM
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D018664:Interleukin-12 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D053762:Interleukin-12 Subunit p40; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D021122:Protein Subunits / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology / Q000473:pathology
D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D018664:Interleukin-12