Differential induction of interleukin-10 and interleukin-12 in dendritic cells by microbial toll-like receptor activators and skewing of T-cell cytokine profiles.
Dendritic cells (DCs) discriminate different microbial pathogens and induce T-cell responses of appropriate effector phenotypes accordingly. Microbial recognition and differentiation are mediated in part by pattern recognition receptors such as Toll-like receptors (TLRs), whereas the development of T-cell effector functions is critically dependent on DC-derived cytokines such as interleukin-12 (IL-12) and IL-10. However, it is not entirely clear to what extent various microbial TLR activators could induce different functional states of DCs that favor different T-cell effector phenotypes. Toward a better understanding of this issue, we examined IL-10 and IL-12 production and T-cell-polarizing potentials of murine bone marrow-derived DCs after stimulation by three microbial TLR activators, namely, lipopolysaccharide (LPS), peptidoglycan (PGN), and zymosan. We found that the three stimuli induced drastically different profiles of IL-10 and IL-12 production in DCs. Further, these stimuli differentially conditioned CD40-dependent IL-10 and IL-12 production by DCs. Finally, LPS-, PGN-, and zymosan-stimulated DCs primed distinct T-cell cytokine profiles. Our results support the notion that microbe-specific information sensed through different TLRs by DCs is linked to differential Th priming through DC-derived cytokines.
Qi
Hai
H
Department of Pathology, University of Texas Medical Branch, Galveston 77555-1070, USA.
Denning
Timothy L
TL
Soong
Lynn
L
D000818:Animals; D019013:CD40 Antigens / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D016753:Interleukin-10 / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D010457:Peptidoglycan / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D051193:Toll-Like Receptors; D015054:Zymosan / Q000494:pharmacology*
D019013:CD40 Antigens; D016207:Cytokines; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D010457:Peptidoglycan; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D016753:Interleukin-10; D018664:Interleukin-12; D015054:Zymosan