Activated macrophages infected with Legionella inhibit T cells by means of MyD88-dependent production of prostaglandins

To understand how macrophages (M phi) activated with IFN-gamma modulate the adaptive immune response to intracellular pathogens, the interaction of IFN-gamma-treated bone marrow-derived murine M phi (BM phi) 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-gamma-treated BM phi, intracellular growth of Legionella was restricted. It was determined that activated BM phi infected with Legionella suppressed IFN-gamma 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 BM phi following Legionella infection. Signaling pathways requiring MyD88 and TLR2 were important for production of a factor produced by IFN-gamma-treated BN phi that interfered with effector T cell functions. Cyclooxygenase-2-dependent production of PGs by IFN-gamma-treated BM phi infected with Legionella was required for inhibition of effector T cell responses. From these data we conclude that activated M phi 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.