Role of IL-18 in the IFN-γ production by innate lymphcytes in response to contact-dependent interaction with dying bacterial-infected macrophages. (55.20)

• Published in: The Journal of immunology (1950) 2012-05, Vol.188 (1_Supplement), p.55-55.20
• Main Author: Kubota, Koichi
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.188.Supp.55.20

We have previously proposed that macrophage cell death caused by bacteria triggers initial IFN-γ production by innate lymphocytes at an early stage of bacterial infection (Scan. J. Immunol. 71:199-209, 2010; Front. Immun. 2:26, 2011). Here we explore the role of IL-18 in this phenomenon by using functional T cell hybridoma B6HO3, a hybrid between YACUT lymphoma and a relevant innate T cell. B6HO3 cells produced IFN-γ dependently of IL-18, but not IL-12p70, in response to cell-cell contact-dependent interaction with dying Listeria monocytogenes (LM)-infected macrophages. Despite the fact that B6HO3 cells required above 300 pg/ml of IL-18 to produce IFN-γ, the amounts of IL-18 secreted by dying LM-infected macrophages were far below this threshold level. IL-18 binding protein (IL-18BP) inhibited this IFN-γ production, but its ED50 was about 30 nM, far exceeding the physiological level of IL-18BP. LPS-primed macrophages, when stimulated with ATP, underwent cell death and secreted the similar amounts of IL-18, but their co-culture with B6HO3 cells did not result in producing IFN-γ. Inhibitors of caspase-1 and cathepsin B did not inhibit LM-infected macrophage cell death, indicating that neither pyroptosis nor pyronecrosis was involved. These results suggest that when macrophages are killed by bacteria, IL-18 plays a pivotal role in the production of IFN-γ by B6HO3 cells through an as yet undefined cell-cell interaction between dying bacterial-infected macrophages and B6HO3 cells.