A novel phenotype for an activated macrophage: the type 2 activated macrophage.
Activated macrophages were used as antigen presenting cells (APCs) to determine the extent to which these APCs could influence an adaptive immune response. We show that activated macrophages induced a strong polarized Th1-like T cell response that was predominated by IFN-gamma. However, when antigen was targeted to Fcgamma receptors on these macrophages, their phenotype changed, and they now induced a T cell response that was predominated by IL-4. The initial biasing by activated macrophages toward a Th1-like response was a result of activation of the innate immune response, as macrophages from MyD88(-/-) mice failed to produce Th1-inducing cytokines. The reversal of the Th1 biasing was a result of FcgammaR ligation, as macrophages lacking the FcR common gamma chain failed to reverse this biasing. To show that this biasing could occur in vivo, mice were injected with activated macrophages or activated macrophages whose FcgammaR had been ligated with an irrelevant immune complex. Mice injected with FcgammaR-ligated macrophages made more antibody than those receiving conventionally activated macrophages, and the antibody was predominantly of the IgG1 isotype. These studies demonstrate that FcgammaR ligation on activated macrophages can change the phenotype of these APCs to cells that preferentially drive a Th2-like response. We have termed these cells type 2 activated macrophages.
Anderson
Charles F
CF
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
Mosser
David M
DM
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017951:Antigen Presentation; D000943:Antigens, Differentiation / Q000235:genetics; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D008262:Macrophage Activation; D008264:Macrophages / Q000145:classification / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D010641:Phenotype; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology; D011971:Receptors, Immunologic / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D016207:Cytokines; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D017452:Receptors, IgG; D011971:Receptors, Immunologic