Activated Macrophages Infected with Legionella Inhibit T Cells by Means of MyD88-Dependent Production of Prostaglandins

Abstract

To understand how macrophages (Mφ) activated with IFN-γ modulate the adaptive immune response to intracellular pathogens, the interaction of IFN-γ-treated bone marrow-derived murine Mφ (BMφ) with Legionella pneumophila was investigated. Although Legionella was able to evade phagosome lysosome fusion initially, and was capable of de novo protein synthesis within IFN-γ-treated BMφ, intracellular growth of Legionella was restricted. It was determined that activated BMφ infected with Legionella suppressed IFN-γ production by Ag-specific CD4 and CD8 T cells. A factor sufficient for suppression of T cell responses was present in culture supernatants isolated from activated BMφ following Legionella infection. Signaling pathways requiring MyD88 and TLR2 were important for production of a factor produced by IFN-γ-treated BMφ that interfered with effector T cell functions. Cyclooxygenase-2-dependent production of PGs by IFN-γ-treated BMφ infected with Legionella was required for inhibition of effector T cell responses. From these data we conclude that activated Mφ can down-modulate Ag-specific T cell responses after they encounter bacterial pathogens through production of PGs, which may be important in preventing unnecessary immune-mediated damage to host tissues.