Activated macrophages infected with Legionella inhibit T cells by means of MyD88-dependent production of prostaglandins.
To understand how macrophages (Mphi) activated with IFN-gamma modulate the adaptive immune response to intracellular pathogens, the interaction of IFN-gamma-treated bone marrow-derived murine Mphi (BMphi) 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 BMphi, intracellular growth of Legionella was restricted. It was determined that activated BMphi 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 BMphi following Legionella infection. Signaling pathways requiring MyD88 and TLR2 were important for production of a factor produced by IFN-gamma-treated BMphi that interfered with effector T cell functions. Cyclooxygenase-2-dependent production of PGs by IFN-gamma-treated BMphi infected with Legionella was required for inhibition of effector T cell responses. From these data we conclude that activated Mphi 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.
Neild
Annie L
AL
Yale University School of Medicine, Section of Microbial Pathogenesis, Boyer Center for Molecular Medicine, New Haven, CT 06536, USA.
Shin
Sunny
S
Roy
Craig R
CR
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000502:physiology*; D000818:Animals; D001854:Bone Marrow Cells; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology; D007876:Legionellosis / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000382:microbiology* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D011453:Prostaglandins / Q000096:biosynthesis*; D037182:T-Cell Antigen Receptor Specificity; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011453:Prostaglandins; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D007371:Interferon-gamma