Department of International Health, Immunology and Microbiology, University of Copenhagen, Panum Institute, Denmark.
Inflamm Bowel Dis. 2010 Mar;16(3):390-400. doi: 10.1002/ibd.21068.
The effect in vitro of six different probiotic strains including Lactobacillus acidophilus NCFM, Lactobacillus salivarius Ls-33, Lactobacillus paracasei subsp. paracasei YS8866441, Lactobacillus plantarum Lp-115, Bifidobacterium bifidum BI-504 and BI-98 was studied on splenic enteroantigen-presenting cells (APC) and CD4(+)CD25(+) T-regulatory cells (Tregs) in splenocyte-T cell proliferation assays.
Splenocytes exposed to enteroantigen +/- probiotics were used to stimulate cultured CD4(+)CD25(-) T cells to which titrated numbers of Tregs were added. Cytokine assays were performed by use of neutralizing antibodies and ELISA.
Exposure of APCs to enteroantigens and the series of probiotic strains mentioned above did not influence the stimulatory capacity of APCs on proliferative enteroantigen-specific T cells. However, exposure to B. bifidum BI-98, BI-504 and L. acidophilus NCFM consistently reduced the suppressive activity of Tregs. The suppressive activity was analyzed using fractionated components of the probiotics, and showed that a component of the cell wall is responsible for the decreased Treg activity in the system. The probiotic-induced suppression of Treg function is not mediated by changes in APC-secretion of the inflammatory cytokines IL-6 or IL-1b.
We conclude that certain probiotic strains can modify APCs to cause reduced Treg activity. This effect apparently depends on a direct APC-to-Treg cell contact. The APC-mediated suppressive effect on Treg function of certain probiotic strains may constrain the anti-inflammatory activity, which is often desired from probiotic therapy. This unexpected function of certain probiotic strains should be taken into consideration when designing adjuvant therapies with these bacteria, or when probiotic strains are selected for improvement of gut-associated inflammation like IBD.
研究了包括嗜酸乳杆菌 NCFM、唾液乳杆菌 Ls-33、副干酪乳杆菌亚种。副干酪乳杆菌 YS8866441、植物乳杆菌 Lp-115、双歧杆菌 BI-504 和 BI-98 在内的 6 种不同益生菌菌株对脾肠抗原呈递细胞 (APC) 和 CD4+CD25+调节性 T 细胞 (Treg) 的体外影响脾细胞-T 细胞增殖试验。
用肠抗原 +/-益生菌处理脾细胞,刺激培养的 CD4+CD25(-)T 细胞,加入滴定数量的 Treg。通过使用中和抗体和 ELISA 进行细胞因子测定。
APC 暴露于肠抗原和上述一系列益生菌菌株不会影响 APC 对增殖肠抗原特异性 T 细胞的刺激能力。然而,暴露于双歧杆菌 BI-98、BI-504 和嗜酸乳杆菌 NCFM 一致降低了 Treg 的抑制活性。使用益生菌的分馏成分分析抑制活性,表明细胞壁的一个成分负责降低该系统中的 Treg 活性。益生菌诱导的 Treg 功能抑制不是由 APC 分泌的炎症细胞因子 IL-6 或 IL-1b 的变化介导的。
我们得出结论,某些益生菌菌株可以修饰 APC 以引起 Treg 活性降低。这种效应显然取决于 APC 与 Treg 细胞的直接接触。某些益生菌菌株对 Treg 功能的 APC 介导抑制作用可能会限制通常从益生菌治疗中获得的抗炎活性。在设计这些细菌的辅助治疗或选择用于改善与肠道相关的炎症(如 IBD)的益生菌菌株时,应考虑某些益生菌菌株的这种意外功能。