T_h 1 and T_h 2 cytokines cooperate to stimulate mannose-receptor-mediated phagocytosis

The mannose receptor is a macrophage surface receptor that mediates both endocytosis and phagocytosis. Previous work has demonstrated that the prototypical T_h 2 cytokine, interleukin-4 (IL-4), increases both cell-surface receptor expression and mannose receptor-mediated endocytosis, whereas the prototypical T_h 1 cytokine, interferon-γ (IFN-γ), decreases both surface expression and endocytosis. In many aspects of the immune response, T_h 1 and T_h 2 cytokines oppose each others' actions. We demonstrate that IL-4 and IFN-γ alone and together enhance mannose receptor-mediated phagocytosis, despite opposing effects on cell-surface mannose receptor expression and endocytosis. Thus these usually antagonistic cytokines cooperate in increasing mannose receptor phagocytic function. The cooperative effect of these cytokines is not observed for Fc receptor-mediated phagocytosis. The T_h 2 cytokine IL-13 exerts similar effects to IL-4. Our results suggest that T_h 1 and T_h 2 cytokines may act in concert at sites of inflammation to enhance mannose receptor-mediated phagocytosis of microorganisms. J. Leukoc. Biol. 64: 108-113; 1998.