Immune response of non-pathogenic Gram(+) and Gram(-) bacteria in inductive sites of the intestinal mucosa Study of the pathway of signaling involved
Immune response of non-pathogenic Gram(+) and Gram(-) bacteria in inductive sites of the intestinal mucosa Study of the pathway of signaling involved
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DOI：
10.1016/j.imbio.2009.01.005
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发表时间：
2010-01-01
期刊：
影响因子：
2.8
通讯作者：
Perdigon, G.
中科院分区：
文献类型：
--
作者：
Dogi, C. A.;Weill, F.;Perdigon, G.
肠道相关淋巴组织 (GALT) 在解剖学和功能上分为诱导部位和效应部位。在之前的工作中，我们证明具有益生菌特性的非致病菌可以改善肠道粘膜免疫系统，增加肠道效应部位产生 IgA 和细胞因子的细胞数量。在目前的工作中，我们研究了非致病性革兰氏(+)、革兰氏(-)细菌和革兰氏(+)益生菌菌株给BALB/c小鼠口服后对诱导位点(PP)的影响。我们还研究了受测菌株在效应位点诱导的一些信号，例如钙调神经磷酸酶和 TLR-9，作为了解此类细菌刺激中诱导机制的一种方式。分析了脂磷壁酸（LTA）在免疫刺激中的作用。所有菌株均增加了PP总群体中IFN-γ和TNF-α(+)细胞的数量，但不增加IL-10(+)细胞的数量。 IFN-γ和TNF-α的释放仅由LPS刺激诱导。所有检测的菌株均增加了钙调磷酸酶(+)细胞的数量，而只有革兰氏(+)菌株增加了TLR-9(+)细胞的数量。在单核巨噬细胞 U937 细胞系上评估了革兰氏阳性菌株纯化 LTA 的免疫刺激特性。这些细胞显示出响应所有以剂量依赖性方式测定的 LTA 的能力，释放 TNF-α 和 IL-10。革兰氏阳性菌株通过能够激活转录因子 NFAT 的钙调神经磷酸酶和 TLR-9 诱导信号。来自 Gram(+) 菌株的 LTA 分子并不是观察到的免疫刺激特性中涉及的唯一结构，特别是对于益生菌菌株。 (C) 2009 爱思唯尔有限公司。版权所有。
The gut associated lymphoid tissue (GALT) is anatomical and functionally divided in inductive and effectors sites. In previous works we demonstrated that non-pathogenic bacteria with probiotic characteristics can improve the gut mucosal immune system, with an increase in the number of IgA and cytokines producing cells in the effector site of the intestine. In the present work we studied the effect of non-pathogenic Gram(+), Gram(-) bacteria and a Gram(+) probiotic strain on the inductor site (PP) after the oral administration to BALB/c mice. We also studied some signals induced by the assayed strain in the effectors site, such as the enzyme calcineurin and TLR-9 as a way to understand the mechanisms induced in such bacterial stimulation. The implicance of the lipoteichoic acid (LTA) in the immunostimulation was analyzed. All strains increased the number of IFN-gamma and TNF-alpha(+) cells, but not of IL-10(+) cells in the total population of PP. The release of IFN-gamma and TNF-alpha was only induced by LPS stimulation. All assayed strains increased the number of calcineurin(+) cells, while only Gram(+) strains increased the number of TLR-9(+) cells. The immunostimulatory properties of the purified LTA from Gram(+) strains was evaluated on a monocyte-macrophage U937 cell line. These cells showed capacity to release TNF-alpha and IL-10 in response to all LTA assayed in a dose-dependent way. Gram(+) strains induced signals through the calcineurin enzyme able to activate the transcriptional factor NFAT and through TLR-9. The LTA molecule from Gram(+) strains would not be the only structure involved in the immunostimulatory properties observed, specially for the probiotic strain. (C) 2009 Elsevier GmbH. All rights reserved.