Sakai Fumihiko, Hosoya Tomohiro, Ono-Ohmachi Aiko, Ukibe Ken, Ogawa Akihiro, Moriya Tomohiro, Kadooka Yukio, Shiozaki Takuya, Nakagawa Hisako, Nakayama Yosuke, Miyazaki Tadaaki
Milk Science Research Institute, Megmilk Snow Brand Co. Ltd., Minamidai, Kawagoe, Saitama, Japan.
Department of Probiotics Immunology, Institute for Genetic Medicine, Hokkaido University, Kita-ku, Sapporo, Japan.
PLoS One. 2014 Aug 21;9(8):e105370. doi: 10.1371/journal.pone.0105370. eCollection 2014.
Probiotic bacteria provide benefits in enhancing host immune responses and protecting against infection. Induction of IgA production by oral administration of probiotic bacteria in the intestine has been considered to be one reason for this beneficial effect, but the mechanisms of the effect are poorly understood. Lactobacillus gasseri SBT2055 (LG2055) is a probiotic bacterium with properties such as bile tolerance, ability to improve the intestinal environment, and it has preventive effects related to abdominal adiposity. In this study, we have found that oral administration of LG2055 induced IgA production and increased the rate of IgA(+) cell population in Peyer's patch and in the lamina propria of the mouse small intestine. The LG2055 markedly increased the amount of IgA in a co-culture of B cells and bone marrow derived dendritic cells (BMDC), and TLR2 signal is critical for it. In addition, it is demonstrated that LG2055 stimulates BMDC to promote the production of TGF-β, BAFF, IL-6, and IL-10, all critical for IgA production from B cells. Combined stimulation of B cells with BAFF and LG2055 enhanced the induction of IgA production. Further, TGF-β signal was shown to be critical for LG2055-induced IgA production in the B cell and BMDC co-culture system, but TGF-β did not induce IgA production in a culture of only B cells stimulated with LG2055. Furthermore, TGF-β was critical for the production of BAFF, IL-6, IL-10, and TGF-β itself from LG2055-stimulated BMDC. These results demonstrate that TGF-β was produced by BMDC stimulated with LG2055 and it has an autocrine/paracrine function essential for BMDC to induce the production of BAFF, IL-6, and IL-10.
益生菌在增强宿主免疫反应和预防感染方面具有益处。口服益生菌在肠道中诱导IgA产生被认为是这种有益作用的一个原因,但该作用的机制尚不清楚。加氏乳杆菌SBT2055(LG2055)是一种益生菌,具有胆汁耐受性、改善肠道环境的能力,并且对腹部肥胖具有预防作用。在本研究中,我们发现口服LG2055可诱导IgA产生,并增加小鼠小肠派尔集合淋巴结和固有层中IgA(+)细胞群体的比例。LG2055在B细胞与骨髓来源的树突状细胞(BMDC)的共培养中显著增加了IgA的量,并且TLR2信号对此至关重要。此外,已证明LG2055刺激BMDC以促进TGF-β、BAFF、IL-6和IL-10的产生,所有这些对于B细胞产生IgA都至关重要。用BAFF和LG2055联合刺激B细胞增强了IgA产生的诱导。此外,TGF-β信号在B细胞和BMDC共培养系统中对LG2055诱导的IgA产生至关重要,但TGF-β在仅用LG2055刺激的B细胞培养中不诱导IgA产生。此外,TGF-β对于LG2055刺激的BMDC产生BAFF、IL-6、IL-10和TGF-β本身至关重要。这些结果表明,TGF-β由LG2055刺激的BMDC产生,并且它具有自分泌/旁分泌功能,这对于BMDC诱导BAFF、IL-6和IL-10的产生至关重要。