Th1 and Th2 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-gamma (IFN-gamma), 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-gamma 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.