Lactobacillus gasseri SBT2055 Induces TGF-β Expression in Dendritic Cells and Activates TLR2 Signal to Produce IgA in the Small Intestine

PLOS ONE, Dec 2019

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.

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Lactobacillus gasseri SBT2055 Induces TGF-β Expression in Dendritic Cells and Activates TLR2 Signal to Produce IgA in the Small Intestine

et al. (2014) Lactobacillus gasseri SBT2055 Induces TGF-b Expression in Dendritic Cells and Activates TLR2 Signal to Produce IgA in the Small Intestine. PLoS ONE 9(8): e105370. doi:10.1371/journal.pone.0105370 Lactobacillus gasseri SBT2055 Induces TGF-b Expression in Dendritic Cells and Activates TLR2 Signal to Produce IgA in the Small Intestine Fumihiko Sakai 0 Tomohiro Hosoya 0 Aiko Ono-Ohmachi 0 Ken Ukibe 0 Akihiro Ogawa 0 Tomohiro Moriya 0 Yukio Kadooka 0 Takuya Shiozaki 0 Hisako Nakagawa 0 Yosuke Nakayama 0 Tadaaki Miyazaki 0 Emiko Mizoguchi, Massachusetts General Hospital, United States of America 0 1 Milk Science Research Institute, Megmilk Snow Brand Co. Ltd. , Minamidai, Kawagoe, Saitama , Japan , 2 Department of Probiotics Immunology, Institute for Genetic Medicine, Hokkaido University , Kita-ku, Sapporo , Japan 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-b, 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-b signal was shown to be critical for LG2055induced IgA production in the B cell and BMDC co-culture system, but TGF-b did not induce IgA production in a culture of only B cells stimulated with LG2055. Furthermore, TGF-b was critical for the production of BAFF, IL-6, IL-10, and TGF-b itself from LG2055-stimulated BMDC. These results demonstrate that TGF-b 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. - Funding: This study was funded by Megmilk Snow Brand Co., Ltd. The funder provided support in the form of salaries for authors (Fumihiko Sakai, Tomohiro Hosoya, Aiko Ono-Ohmachi, Ken Ukibe, Akihiro Ogawa, Tomohiro Moriya, and Yukio Kadooka), but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the author contributions section. Competing Interests: Fumihiko Sakai, Tomohiro Hosoya, Aiko Ono-Ohmachi, Ken Ukibe, Akihiro Ogawa, Tomohiro Moriya, and Yukio Kadooka are employees of Megmilk Snow Brand Co., Ltd. There are no other patents, products in development or marketed products to declare. This does not alter the authors adherence to all the PLOS ONE policies on sharing data and materials. . These authors contributed equally to this work. Probiotics are live microorganisms which when they are administered in adequate amounts confer health benefits to the host [1]. Probiotic bacteria, mainly belonging to the class of lactic acid bacteria (LAB), are well known to induce beneficial effects in human and animal health. In particular, lactobacilli are characterized by the production of lactic acid and are commonly applied to many vegetable, meat, and dairy fermentations. These bacteria can influence the composition and activity of the gut microbiota. Currently, there is a general consensus that orally administered probiotic bacteria contribute to immune homeostasis by altering the microbial balance or by interacting with the host immune system [24]. In particular, the interplay between the mucosaassociated immune system and microbiota certainly plays a pivotal role in mucosal tissue homeostasis as well as in protection against infectious and inflammatory diseases occurring at mucosal sites [5]. In the intestinal tract, IgA is the most abundant immunoglobulin isotype, with up to 3 g of secretory IgA secreted into the human intestinal lumen per day [6,7]. The IgA plays an important role in the host defense against mucosally transmitted pathogens, preventing commensal bacteria from binding to epithelial cells, and neutralizing their toxins to maintain homeostasis at the mucosal surfaces [8]. These functions are beneficial for the host as they reduce the risk of infection and maintain an intestinal environment accommodating to the appropriate commensal population. In humans, individuals with IgA defi (...truncated)


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Fumihiko Sakai, Tomohiro Hosoya, Aiko Ono-Ohmachi, Ken Ukibe, Akihiro Ogawa, Tomohiro Moriya, Yukio Kadooka, Takuya Shiozaki, Hisako Nakagawa, Yosuke Nakayama, Tadaaki Miyazaki. Lactobacillus gasseri SBT2055 Induces TGF-β Expression in Dendritic Cells and Activates TLR2 Signal to Produce IgA in the Small Intestine, PLOS ONE, 2014, 8, DOI: 10.1371/journal.pone.0105370