Differential roles of segmented filamentous bacteria and clostridia in development of the intestinal immune system
Differential roles of segmented filamentous bacteria and clostridia in development of the intestinal immune system
复制标题
DOI：
10.1128/iai.67.7.3504-3511.1999
复制
发表时间：
1999-07-01
影响因子：
3.1
通讯作者：
Itoh, K
中科院分区：
文献类型：
--
作者：
Umesaki, Y;Setoyama, H;Itoh, K
消化道中微生物群落的存在促进肠道免疫系统的发育。在本研究中，为了评估两种本土微生物——分别栖息于小肠和大肠的分节丝状菌（SFB）和梭菌在这种免疫发育中的作用，我们分别分析了感染SFB、梭菌以及同时感染SFB和梭菌的三种无菌小鼠，并与无特定病原体菌群的无菌（GF）小鼠或常规化（Cvd）小鼠进行比较。在小肠中，与SFB相关的小鼠（SFB - 小鼠）中带有αβ T细胞受体的上皮内淋巴细胞（αβ IEL）数量增加，而在与梭菌相关的小鼠（Clost - 小鼠）中则没有增加。在GF小鼠、Cvd小鼠以及这些无菌小鼠之间，Vβ的使用没有很大差异，尽管与SFB相关联在一定程度上降低了CD8β⁻亚群中Vβ6⁺细胞的比例，与GF小鼠相比。在SFB - 小鼠中观察到上皮细胞上主要组织相容性复合体II类分子的表达，但在Clost - 小鼠中没有观察到。另一方面，在大肠中，αβ IEL中CD4⁻CD8⁺细胞数量与CD4⁺CD8⁻细胞数量的比值在Clost - 小鼠中增加，而在SFB - 小鼠中没有增加。当同时与SFB和梭菌相关联时，小肠和大肠中IEL的数量和表型发生变化，变得与Cvd小鼠相似。特别是，αβ IEL中CD8αβ⁺细胞数量与CD8αα⁺细胞数量的比值在SFB - 小鼠的小肠中异常升高，在同时感染SFB和梭菌时降低到Cvd小鼠的水平。固有层中产生免疫球蛋白A（IgA）的细胞数量在SFB - 小鼠中比在Clost - 小鼠中更高，不仅在回肠中，在结肠中也是如此。与GF小鼠相比，Clost - 小鼠结肠中产生IgA的细胞数量略有增加。综上所述，SFB和梭菌分别促进小肠中IEL和产生IgA的细胞的发育以及大肠中仅IEL的发育，这表明小肠和大肠之间对本土细菌的免疫反应存在分区现象。
The presence of microflora in the digestive tract promotes the development of the intestinal immune system. In this study, to evaluate the roles of two types of indigenous microbe, segmented filamentous bacteria (SFB) and clostridia, whose habitats are the small and large intestines, respectively, in this immunological development, we analyzed three kinds of gnotobiotic mice contaminated with SFB, clostridia, and both SFB and clostridia, respectively, in comparison with germfree (GF) or conventionalized (Cvd) mice associated with specific-pathogen-free flora. In the small intestine, the number of alpha beta T-cell receptor-bearing intraepithelial lymphocytes (alpha beta IEL) increased in SFB-associated mice (SFB-mice) but not in clostridium-associated mice (Clost-mice). There was no great difference in V beta usage among GF mice, Cvd mice, and these gnotobiotic mice, although the association with SFB decreased the proportion of V beta 6(+) cells in CD8 beta(-) subsets to some extent, compared to that in GF mice. The expression of major histocompatibility complex class II molecules on the epithelial cells was observed in SFB-mice but not in Clost-mice. On the other hand, in the large intestine, the ratio of the number of CD4(-) CD8(+) cells to that of CD4(+) CD8(-) cells in alpha beta IEL increased in Clost-mice but not in SFB-mice. On association with both SFB and clostridia, the numbers and phenotypes of IEL in the small and large intestines changed to become similar to those in Cvd mice. In particular, the ratio of the number of CD8 alpha beta(+) cells to that of CD8 alpha alpha(+) cells in alpha beta IEL, unusually elevated in the small intestines of SFB-mice, decreased to the level in Cvd mice on contamination with both SFB and clostridia. The number of immunoglobulin A (IgA)-producing cells in the lamina propria was more elevated in SFB-mice than in Clost-mice, not only in the ileum but also in the colon. The number of IgA-producing cells in the colons of Clost-mice was a little increased compared to that in GF mice. Taken together, SFB and clostridia promoted the development of both IEL and IgA-producing cells in the small intestine and that of only IEL in the large intestine, respectively, suggesting the occurrence of compartmentalization of the immunological responses to the indigenous bacteria between the small and large intestines.