TLR Agonists That Induce IFN-β Abrogate Resident Macrophage Suppression of T Cells

Resident tissue macrophages (M phi s) continually survey the microenvironment, ingesting Ags and presenting them on their surface for recognition by T cells. Because these Ags can be either host cell-or pathogen-derived, M phi s must be able to distinguish whether a particular Ag should provoke an immune response or be tolerated. However, the mechanisms that determine whether M phi s promote or inhibit T cell activation are not well understood. To investigate this, we first determined the mechanism by which murine resident peritoneal M phi s suppress in vitro T cell proliferation in the absence of pathogens and then explored the effects of different pathogen-derived molecules on M phi immunosuppression. Our results suggest that, in response to IFN-gamma, which is secreted by TCR-activated T cells, resident peritoneal M phi s acquire immunosuppressive properties that are mediated by NO. However, pretreatment of M phi s with LPS or dsRNA, but not CpG or peptidoglycan, eliminates their suppressive properties, in part via the induction of autocrine-acting IFN-beta. These results suggest TLR agonists that activate TRIF, and consequently induce IFN-beta, but not those that exclusively signal through MyD88, abrogate the immunosuppressive properties of M phi s, and thus promote T cell expansion and elimination of invading microorganisms. The Journal of Immunology, 2010, 185: 4545-4553.