Secretion of interferon-γ by human macrophages demonstrated at the single-cell level after costimulation with interleukin (IL)-12 plus IL-18
Secretion of interferon-γ by human macrophages demonstrated at the single-cell level after costimulation with interleukin (IL)-12 plus IL-18
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DOI：
10.1111/j.1365-2567.2008.02905.x
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发表时间：
2009-03-01
期刊：
影响因子：
6.4
通讯作者：
Bofill, Margarita
中科院分区：
文献类型：
--
作者：
Darwich, Laila;Coma, Gemma;Bofill, Margarita
免疫应答的干扰素（IFN）-γ组分在对抗感染性和非感染性疾病中起着重要作用。在针对病原体的适应性免疫应答中，通过与白细胞介素（IL）-12和IL-18的协同共刺激诱导人T细胞和自然杀伤（NK）细胞分泌IFN-γ已得到充分证实，但在巨噬细胞中诱导类似活性仍存在争议，疑虑主要集中在相关实验中巨噬细胞被NK或T细胞污染。然而，巨噬细胞对IFN应答的可能贡献是与许多疾病的发病机制相关的重要因素。为了解决这个问题，我们通过免疫组织化学和酶联免疫吸附斑点（ELISPOT）分析在单细胞水平上分析IFN-γ的产生，并明确地证明，通过用IL-12和IL-18或巨噬细胞集落刺激因子（M-CSF）的组合刺激，体外来源于单核细胞的人巨噬细胞能够产生IFN-γ。当进一步用IL-12和IL-18的组合刺激时，此外，天然活化的肺泡巨噬细胞在用IL-12和IL-18处理后立即分泌IFN-γ。因此，除了淋巴样细胞之外，人巨噬细胞也有助于IFN-γ应答，提供了先天性和获得性免疫应答之间的另一种联系。
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.