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. 2006 Jun 15;176(12):7438-46.
doi: 10.4049/jimmunol.176.12.7438.

V体育2025版 - T cell-independent, TLR-induced IL-12p70 production in primary human monocytes

Isabelle Bekeredjian-Ding  1 , Susanne Ilona Roth, Stefanie Gilles, Thomas Giese, Andrea Ablasser, Veit Hornung, Stefan Endres, Gunther Hartmann
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V体育2025版 - T cell-independent, TLR-induced IL-12p70 production in primary human monocytes

Isabelle Bekeredjian-Ding et al. J Immunol. .

Abstract

IL-12p70 is a key cytokine for the induction of Th1 immune responses. IL-12p70 production in myeloid cells is thought to be strictly controlled by T cell help. In this work we demonstrate that primary human monocytes can produce IL-12p70 in the absence of T cell help. We show that human monocytes express TLR4 and TLR8 but lack TLR3 and TLR7 even after preincubation with type I IFN. Simultaneous stimulation of TLR4 and TLR8 induced IL-12p70 in primary human monocytes. IL-12p70 production in peripheral blood myeloid dendritic cells required combined stimulation of TLR7/8 ligands together with TLR4 or with TLR3 ligands. In the presence of T cell-derived IL-4, but not IFN-gamma, stimulation with TLR7/8 ligands was sufficient to stimulate IL-12p70 production VSports手机版. In monocytes, type I IFN was required but not sufficient to costimulate IL-12p70 induction by TLR8 ligation. Furthermore, TLR8 ligation inhibited LPS-induced IL-10 in monocytes, and LPS alone gained the ability to stimulate IL-12p70 in monocytes when the IL-10 receptor was blocked. Together, these results demonstrate that monocytes are licensed to synthesize IL-12p70 through type I IFN provided via the Toll/IL-1R domain-containing adaptor inducing IFN-beta pathway and the inhibition of IL-10, both provided by combined stimulation with TLR4 and TLR8 ligands, triggering a potent Th1 response before T cell help is established. .

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