CD8- DCs induce IL-12-independent Th1 differentiation through Delta 4 Notch-like ligand in response to bacterial LPS.
Toll-like receptor (TLR) ligation is believed to skew T cell responses toward T helper (Th)1 differentiation by inducing interleukin (IL)-12 secretion by CD8(+) dendritic cells (DCs). However, TLR-dependent Th1 responses occur in the absence of IL-12. To determine how DCs induce Th1 differentiation in the absence of IL-12, we examined the response of IL-12-deficient DCs to bacterial lipopolysaccharide (LPS). We find that LPS activates MyD88-dependent Delta 4 Notch-like ligand expression by CD8(-) DCs, and that these cells direct Th1 differentiation by an IL-12-independent and Notch-dependent mechanism in vitro and in vivo. Thus, activation of the two DC subsets by TLR4 leads to Th1 responses by two distinct MyD88-dependent pathways.
Skokos
Dimitris
D
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10021, USA.
Nussenzweig
Michel C
MC
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology*; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology*; D018664:Interleukin-12 / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D010957:Plasmids; D051880:Receptors, Notch / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D016827:CD8 Antigens; D002135:Calcium-Binding Proteins; C519665:DLL4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008070:Lipopolysaccharides; D008565:Membrane Proteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D051880:Receptors, Notch; D051193:Toll-Like Receptors; D018664:Interleukin-12