Differential regulation of interleukin 12 and interleukin 23 production in human dendritic cells.
We analyzed interleukin (IL) 12 and IL-23 production by monocyte-derived dendritic cells (mono-DCs). Mycobacterium tuberculosis H37Rv and zymosan preferentially induced IL-23. IL-23 but not IL-12 was efficiently induced by the combination of nucleotide-binding oligodimerization domain and Toll-like receptor (TLR) 2 ligands, which mimics activation by M. tuberculosis, or by the human dectin-1 ligand beta-glucan alone or in combination with TLR2 ligands, mimicking induction by zymosan. TLR2 ligands inhibited IL-12 and increased IL-23 production. DC priming with interferon (IFN) gamma strongly increased IL-12 production, but was not required for IL-23 production and inhibited IL-23 production induced by beta-glucan. The pattern of IL-12 and IL-23 induction was reflected in accumulation of the IL-12p35 and IL-23p19 transcripts, respectively, but not IL-12/23p40. Although IL-23, transforming growth factor beta, and IL-6 contained in the supernatants of activated mono-DCs played a role in the induction of IL-17 by human CD4(+) T cells, IL-1beta, in combination with one or more of those factors, was required for IL-17 production, and its production determined the differential ability of the stimuli used to elicit mono-DCs to produce soluble factors directing IL-17 production. Thus, the differential ability of pathogens to induce antigen-presenting cells to produce cytokines regulates the immune response to infection.
Gerosa
Franca
F
Department of Pathology, Section of Immunology, University of Verona, 37134 Verona, Italy. franca.gerosa@univr.it
Baldani-Guerra
Barbara
B
Lyakh
Lyudmila A
LA
Batoni
Giovanna
G
Esin
Semih
S
Winkler-Pickett
Robin T
RT
Consolaro
Maria Rita
MR
De Marchi
Mario
M
Giachino
Daniela
D
Robbiano
Angela
A
Astegiano
Marco
M
Sambataro
Angela
A
Kastelein
Robert A
RA
Carra
Giuseppe
G
Trinchieri
Giorgio
G
D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D018664:Interleukin-12 / Q000235:genetics*; D053759:Interleukin-23 / Q000235:genetics*; D008715:Methionine / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000502:physiology; D015054:Zymosan / Q000494:pharmacology
D053759:Interleukin-23; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D018664:Interleukin-12; D007371:Interferon-gamma; D015054:Zymosan; D008715:Methionine