Gary-Gouy Hélène, Lebon Pierre, Dalloul Ali H
Laboratoire d'Immunologie, INSERM U 543, Hôpital Pitié-Salpêtrière, Université de Paris VI, 75013 Paris, France.
J Interferon Cytokine Res. 2002 Jun;22(6):653-9. doi: 10.1089/10799900260100132.
The principal interferon-alpha/beta (IFN-I)-producing cells are plasmacytoid dendritic cell (PDC) precursors belonging to the lymphoid lineage. Monocytes that can differentiate into dendritic cells (DC) also produce IFN-I, although much less than PDC, after interaction with infectious agents. We show that whereas viruses trigger these cells to produce IFN-I, the amount of IFN is tightly controlled by cytokines. Monocytes produced IFN-I in response to Sendai virus (SV) infection, and PDC responded to both SV and herpes simplex virus (HSV). All cytokines tested failed to induce production of IFN-I in the absence of infection. However, among 18 relevant cytokines, incubation of PDC with interleukin-4 (IL-4), IL-15, and IL-7 alone or in combination with IL-3 before infection, enhanced IFN-I secretion. At variance, IL-12 alone or in synergy with granulocyte-macrophage colony-stimulating factor (GM-CSF) was active on SV-infected but not on HSV-infected monocytes. Tumor necrosis factor-alpha (TNF-alpha) and IL-4 inhibited IFN-I production by PDC and monocytes, respectively, and IL-10 strongly inhibited IFN-I production in both cell lineages. The response of PDC to IL-7 and IL-15, which also activate natural killer (NK) cell maturation, further emphasizes the cooperation between these two cell subsets in the control of innate immunity.
主要产生Ⅰ型干扰素(IFN-Ⅰ)的细胞是属于淋巴谱系的浆细胞样树突状细胞(pDC)前体。能够分化为树突状细胞(DC)的单核细胞在与感染因子相互作用后也会产生IFN-Ⅰ,尽管其产生量远低于pDC。我们发现,病毒可触发这些细胞产生IFN-Ⅰ,而IFN的量则受到细胞因子的严格调控。单核细胞在感染仙台病毒(SV)后产生IFN-Ⅰ,而pDC对SV和单纯疱疹病毒(HSV)均有反应。在未感染的情况下,所有测试的细胞因子均未能诱导IFN-Ⅰ的产生。然而,在18种相关细胞因子中,在感染前单独用白细胞介素-4(IL-4)、IL-15和IL-7或与IL-3联合孵育pDC,可增强IFN-Ⅰ分泌。与之不同的是,单独的IL-12或与粒细胞-巨噬细胞集落刺激因子(GM-CSF)协同作用,对感染SV的单核细胞有活性,但对感染HSV的单核细胞无活性。肿瘤坏死因子-α(TNF-α)和IL-4分别抑制pDC和单核细胞产生IFN-Ⅰ,而IL-10强烈抑制这两种细胞谱系产生IFN-Ⅰ。pDC对IL-7和IL-15的反应,这两种细胞因子也可激活自然杀伤(NK)细胞成熟,进一步强调了这两个细胞亚群在先天免疫控制中的合作。