Secretion of interferon‐γ by human macrophages demonstrated at the single‐cell level after costimulation with interleukin (IL)‐12 plus IL‐18

作者：Laila Darwich, Gemma Coma, Ruth Peña, Rocío Bellido, Ester J. J. Blanco, José A. Esté, Francesc Enric Borràs, Bonaventura Clotet, Lidia Ruíz, Antoni Rosell, Felipe Andreo, R. M. E. Parkhouse, Margarita Bofill · 发表于：Immunology · 年份：2008 · DOI：10.1111/j.1365-2567.2008.02905.x · 被引用次数：229 · 研究领域：Immune Cell Function and Interaction、Inflammasome and immune disorders、Immune Response and Inflammation

The interferon (IFN)-gamma component of the immune response plays an essential role in combating infectious and non-infectious diseases. Induction of IFN-gamma secretion by human T and natural killer (NK) cells through synergistic costimulation with interleukin (IL)-12 and IL-18 in the adaptive immune responses against pathogens is well established, but induction of similar activity in macrophages is still controversial, with doubts largely focusing on contamination of macrophages with NK or T cells in the relevant experiments. The possible contribution of macrophages to the IFN response is, however, an important factor relevant to the pathogenesis of many diseases. To resolve this issue, we analysed the production of IFN-gamma at the single-cell level by immunohistochemistry and by enzyme-linked immunosorbent spot (ELISPOT) analysis and unequivocally demonstrated that human macrophages derived from monocytes in vitro through stimulation with a combination of IL-12 and IL-18 or with macrophage colony-stimulating factor (M-CSF) were able to produce IFN-gamma when further stimulated with a combination of IL-12 and IL-18. In addition, naturally activated alveolar macrophages immediately secreted IFN-gamma upon treatment with IL-12 and IL-18. Therefore, human macrophages in addition to lymphoid cells contribute to the IFN-gamma response, providing another link between the innate and acquired immune responses.