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)