Ceramide Inhibits Antigen Uptake and Presentation by Dendritic Cells

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  • Federica Sallusto
    From the *Department of Immunology, Istituto Superiore di Sanità, 00161 Rome; and ‡Department of Experimental Medicine and Biochemical Sciences, University of Tor Vergata, 00133 Rome, Italy
  • Chiara Nicolò
    From the *Department of Immunology, Istituto Superiore di Sanità, 00161 Rome; and ‡Department of Experimental Medicine and Biochemical Sciences, University of Tor Vergata, 00133 Rome, Italy
  • Ruggero De Maria
    From the *Department of Immunology, Istituto Superiore di Sanità, 00161 Rome; and ‡Department of Experimental Medicine and Biochemical Sciences, University of Tor Vergata, 00133 Rome, Italy
  • Silvia Corinti
    From the *Department of Immunology, Istituto Superiore di Sanità, 00161 Rome; and ‡Department of Experimental Medicine and Biochemical Sciences, University of Tor Vergata, 00133 Rome, Italy
  • Roberto Testi
    From the *Department of Immunology, Istituto Superiore di Sanità, 00161 Rome; and ‡Department of Experimental Medicine and Biochemical Sciences, University of Tor Vergata, 00133 Rome, Italy

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<jats:p>Ceramides are intramembrane diffusible mediators involved in transducing signals originated from a variety of cell surface receptors. Different adaptive and differentiative cellular responses, including apoptotic cell death, use ceramide-mediated pathways as an essential part of the program. Here, we show that human dendritic cells respond to CD40 ligand, as well as to tumor necrosis factor-α and IL-1β, with intracellular ceramide accumulation, as they are induced to differentiate. Dendritic cells down-modulate their capacity to take up soluble antigens in response to exogenously added or endogenously produced ceramides. This is followed by an impairment in presenting soluble antigens to specific T cell clones, while cell viability and the capacity to stimulate allogeneic responses or to present immunogenic peptides is fully preserved. Thus, ceramide-mediated pathways initiated by different cytokines can actively modulate professional antigen-presenting cell function and antigen-specific immune responses.</jats:p>

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