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 bo th endocytosis and phagocytosis. Previous work has demonstrated that t he prototypical T(h)2 cytokine, interleukin-4 (IL-4), increases both c ell-surface receptor expression and mannose receptor-mediated endocyto sis, whereas the prototypical T(h)1 cytokine, interferon-gamma (IFN-ga mma), decreases both surface expression and endocytosis, In many aspec ts of the immune response, T(h)1 and T(h)2 cytokines oppose each other s' actions, We demonstrate that IL-4 and IFN-gamma alone and together enhance mannose receptor-mediated phagocytosis, despite opposing effec ts on cell-surface mannose receptor expression and endocytosis, Thus t hese usually antagonistic cytokines cooperate in increasing mannose re ceptor phagocytic function. The cooperative effect of these cytokines is not observed for Fc receptor-mediated phagocytosis, The T(h)2 cytok ine 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.