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 Th2 cytokine, interleukin-4 (IL-4), increases both cell-surface receptor expression and mannose receptor-mediated endocytosis, whereas the prototypical Th1 cytokine, interferon-gamma (IFN-gamma), decreases both surface expression and endocytosis. In many aspects of the immune response, Th1 and Th2 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 Th2 cytokine IL-13 exerts similar effects to IL-4. Our results suggest that Th1 and Th2 cytokines may act in concert at sites of inflammation to enhance mannose receptor-mediated phagocytosis of microorganisms.
Raveh
D
D
Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Kruskal
B A
BA
Farland
J
J
Ezekowitz
R A
RA
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D004347:Drug Interactions; D007371:Interferon-gamma / Q000494:pharmacology*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D037181:Lectins, C-Type; D008264:Macrophages / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D013268:Stimulation, Chemical; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
D000970:Antineoplastic Agents; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D015847:Interleukin-4; D007371:Interferon-gamma