Cross Martin L, Ganner Anja, Teilab Diaa, Fray Linley M
Human Nutrition and Health Research Group, Institute of Food, Nutrition and Human Health, Massey University, Riddet Building, Level 2, Palmerston North, New Zealand.
FEMS Immunol Med Microbiol. 2004 Oct 1;42(2):173-80. doi: 10.1016/j.femsim.2004.04.001.
Bacteria used in commercial probiotic preparations are most commonly gram-positive lactic acid-producing species, although there are also some probiotic products which utilise gram-negative coliform bacteria. Characterising how the innate immune system responds to these bacteria in vitro may give an indication as to the likely immunomodulatory events that can be triggered following probiotic administration in vivo. Here, an established gram-positive probiotic (Lactobacillus casei Shirota) was compared against a novel gram-negative probiotic strain (Escherichia coli Nissle 1917) for its ability to induce cytokine production in a cell type representative of the innate immune system; in addition, responses were contrasted against those induced by an enteropathogenic coliform, E. coli 2282. We investigated the ability of these three bacterial strains to modulate production of interleukins-10, -12 and -18; tumour necrosis factor-alpha; interferon-alpha; and transforming growth factor-beta, via a series of in vitro culture experiments involving the murine monocyte/macrophage cell line J774A.1. All bacteria induced marked secretion of IL-12 and TNFalpha by cells, while only coliforms induced production of IL-10; there was minimal or no induction of IL-18 or TGFbeta. Activation of cells with recombinant gamma-interferon promoted increased production of IL-12, but decreased production of IL-10, in response to the co-culture of coliform bacteria, indicating differential cytokine induction depending on the activation status of the target cell. In general, live bacteria stimulated higher levels of IL-10, IL-12 and TNFalpha secretion than heat-killed preparations, while only live coliforms induced IFNalpha. These findings are discussed in relation to the likely immunomodulatory effects of gram-positive and gram-negative bacteria on the innate immune system in vivo, with particular emphasis on the marked similarity in cytokine response patterns observed between probiotic versus pathogenic coliform bacteria.
商业益生菌制剂中使用的细菌最常见的是革兰氏阳性产乳酸菌种，不过也有一些益生菌产品使用革兰氏阴性大肠菌。在体外表征先天免疫系统对这些细菌的反应，可能会提示在体内施用益生菌后可能引发的免疫调节事件。在此，将一种已确立的革兰氏阳性益生菌（干酪乳杆菌代田株）与一种新型革兰氏阴性益生菌菌株（大肠杆菌Nissle 1917）进行比较，以研究它们在代表先天免疫系统的细胞类型中诱导细胞因子产生的能力；此外，还将其反应与一种肠道致病性大肠菌大肠杆菌2282诱导的反应进行对比。我们通过一系列涉及小鼠单核细胞/巨噬细胞系J774A.1的体外培养实验，研究了这三种细菌菌株调节白细胞介素-10、-12和-18、肿瘤坏死因子-α、干扰素-α以及转化生长因子-β产生的能力。所有细菌均诱导细胞显著分泌IL-12和TNFα，而只有大肠菌诱导IL-10的产生；IL-18或TGFβ的诱导作用极小或没有。用重组γ干扰素激活细胞，会促进在与大肠菌共培养时IL-12产生增加，但IL-10产生减少，这表明根据靶细胞的激活状态，细胞因子诱导存在差异。一般来说，活细菌比热灭活制剂刺激更高水平的IL-10、IL-12和TNFα分泌，而只有活大肠菌诱导IFNα。结合革兰氏阳性和革兰氏阴性细菌对体内先天免疫系统可能的免疫调节作用对这些发现进行了讨论，特别强调了益生菌与致病性大肠菌之间观察到的细胞因子反应模式的显著相似性。
