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CCR5 provides a signal for microbial induced production of IL-12 by CD8α+ dendritic cells

Nature Immunology volume 1, pages 83–87 (2000)Cite this article

Abstract

The activation of dendritic cells (DC) to produce interleukin 12 (IL-12) is thought to be a key step in the initiation of cell-mediated immunity to intracellular pathogens. Here we show that ligation of the C–C chemokine receptor (CCR) 5 can provide a major signal for the induction of IL-12 synthesis by the CD8α+ subset of DC and that this pathway is important in establishing interferon γ-dependent resistance to the protozoan parasite Toxoplasma gondii. These findings support the concept that the early induction of chemokines by invading pathogens is a critical step not only for the recruitment of DC but also for the determination of their subsequent immunologic function.

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Figure 1: Defective STAg-induced splenic DC clustering and IL-12 production in mice pre-treated with Met-RANTES or genetically deficient in CCR5.
Figure 2: STAg induction of CCR5 ligand expression in vivo and in vitro.
Figure 3: Dependence on CCR5 of in vivo IL-12 production by CD8α+ DC.
Figure 4: Partial role of CCR5 in STAg-induced IL-12 production by DC in vitro.
Figure 5: CCR5 ligands induce IL-12 production by splenic CD8α+ DC in vitro.

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Acknowledgements

We thank R. Swofford for performing FACS purification of DC as well as R. Germain, D. Sacks and J. Farber for their comments on this manuscript.

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Authors and Affiliations

  1. Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    Julio Aliberti, Marco Schito, Sara Hieny & Alan Sher

  2. Immunobiology Laboratory, Imperial Cancer Research Fund, London, UK

    Caetano Reis e Sousa

  3. Ares-Serono Pharmaceutical Research Institute S.A, Geneva, Switzerland

    Timothy Wells

  4. Departments of Pulmonary Medicine and Microbiology/Immunology, University of Michigan Medical Center, Ann Arbor, MI, USA

    Gary B. Huffnagle

Authors
  1. Julio Aliberti
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  2. Caetano Reis e Sousa
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Correspondence to Julio Aliberti.

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Aliberti, J., Reis e Sousa, C., Schito, M. et al. CCR5 provides a signal for microbial induced production of IL-12 by CD8α+ dendritic cells. Nat Immunol 1, 83–87 (2000). https://doi.org/10.1038/76957

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