IMMUNE-COMPLEXES INHIBIT ANTIMICROBIAL RESPONSES THROUGH INTERLEUKIN-10 PRODUCTION - EFFECTS IN SEVERE COMBINED IMMUNODEFICIENT MICE DURING LISTERIA INFECTION

IMMUNE-COMPLEXES INHIBIT ANTIMICROBIAL RESPONSES THROUGH INTERLEUKIN-10 PRODUCTION - EFFECTS IN SEVERE COMBINED IMMUNODEFICIENT MICE DURING LISTERIA INFECTION
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DOI:
10.1172/jci117837
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发表时间:
1995-04-01
影响因子:
15.9
通讯作者:
UNANUE, ER
UNANUE, ER
中科院分区:
医学1区
文献类型:
--
作者:
TRIPP, CS;BECKERMAN, KP;UNANUE, ER

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可溶性抗原-抗体复合物的存在使小鼠极易感染细胞内病原体单核细胞增生李斯特菌,在这份报告中,我们表明,这种抑制是明显的先天免疫反应的水平,并介导的IL-10。与免疫活性小鼠一样,注射免疫复合物的严重联合免疫缺陷突变(SCID)小鼠死于亚致死剂量的L。单核细胞增多症如果用IL-10的中和抗体预处理,这些小鼠受到保护。在体外,免疫复合物刺激SCID脾细胞和脾巨噬细胞产生IL-10。同样,免疫复合物抑制与热灭活-L培养的SCID脾细胞产生TNF和IFN-γ。这种抑制通过中和IL-10而不是IL-4或TGF-β来逆转。免疫复合物和rIL-10抑制细胞因子的产生,如果之前或同时加入热杀死的-L的SCID脾细胞。这些数据支持免疫复合物通过刺激巨噬细胞产生IL-10来调节宿主防御和免疫应答的模型。
The presence of soluble antigen-antibody complexes renders mice highly susceptible to infection with the intracellular pathogen Listeria monocytogenes, In this report we show that this inhibition is manifest at the level of the innate immune response and is mediated by IL-10. Like immunocompetent mice, mice with the severe combined immunodeficient mutation (SCID) injected with immune complexes died from a sublethal dose of L. monocytogenes. These mice were protected if pretreated with neutralizing antibodies to IL-10. In vitro, immune complexes stimulated IL-10 production by SCID splenocytes and splenic macrophages. Likewise, immune complexes inhibited TNF and IFN-gamma production by SCID splenocytes cultured with heat-killed-L. monocytogenes, This inhibition was reversed by neutralization of IL-10 but not IL-4 or TGF-beta. Immune complexes and rIL-10 inhibited cytokine production by SCID splenocytes if added before or simultaneously with heat-killed-L. monocytogenes, These data support a model in which immune complexes modulate host defense and the immune response by stimulating the production of IL-10 from macrophages.