Department of Food Bioscience and Biotechnology, College of Bioresource Sciences, Nihon University, Kanagawa 252-0880, Japan.
Immunobiology. 2013 Apr;218(4):645-51. doi: 10.1016/j.imbio.2012.07.033. Epub 2012 Aug 8.
It has been demonstrated that intestinal commensal bacteria induce immunoglobulin (Ig) A production by promoting the development of gut-associated lymphoid tissues in the small intestine. However, the precise mechanism whereby these bacteria modulate IgA production in the large intestine, which harbors the majority of intestinal commensals, is poorly understood. In addition, it is not known which commensal bacteria induce IgA production in the small intestine and which induce production in the large intestine. To address these issues, we generated gnotobiotic mice mono-associated with different murine commensal bacteria by inoculating germ-free (GF) mice with Lactobacillus johnsonii or Bacteroides acidifaciens. In GF mice, IgA production was barely detectable in the small intestine and was not detected in the large intestine. Interestingly, total IgA secretion in the large intestinal mucosa of B. acidifaciens mono-associated (BA) mice was significantly greater than that of GF and L. johnsonii mono-associated (LJ) mice. However, there was no difference in total IgA production in the small intestine of GF, LJ and BA mice. In addition, in the large intestine of BA mice, the expression of IgA(+) cells and germinal center formation were more remarkable than in GF and LJ mice. Furthermore, B. acidifaciens-specific IgA was detected in the large intestine of BA mice. These results suggest that the production of IgA in the large intestine may be modulated by a different mechanism than that in the small intestine, and that B. acidifaciens is one of the predominant bacteria responsible for promoting IgA production in the large intestine.
已证实,肠道共生菌通过促进小肠中肠相关淋巴组织的发育来诱导免疫球蛋白(Ig)A 的产生。然而,这些细菌在大肠中调节 IgA 产生的确切机制(其中含有大多数肠道共生菌)仍知之甚少。此外,尚不清楚哪些共生菌在小肠中诱导 IgA 产生,哪些在大肠中诱导 IgA 产生。为了解决这些问题,我们通过将格氏乳杆菌或普通拟杆菌接种于无菌(GF)小鼠,使无菌小鼠单定植不同的鼠共生菌,从而生成单定植共生菌的无菌小鼠。在 GF 小鼠中,几乎检测不到小肠中的 IgA 产生,也检测不到大肠中的 IgA 产生。有趣的是,B. acidifaciens 单定植(BA)小鼠的大肠黏膜总 IgA 分泌量明显大于 GF 和 L. johnsonii 单定植(LJ)小鼠。然而,GF、LJ 和 BA 小鼠的小肠总 IgA 产生量没有差异。此外,在 BA 小鼠的大肠中,IgA(+)细胞的表达和生发中心的形成比 GF 和 LJ 小鼠更为显著。此外,在 BA 小鼠的大肠中检测到了针对 B. acidifaciens 的特异性 IgA。这些结果表明,大肠中 IgA 的产生可能受到与小肠不同的机制调节,并且 B. acidifaciens 是促进大肠中 IgA 产生的主要细菌之一。