TY - JOUR
T1 - Exopolysaccharides From Streptococcus thermophilus ST538 Modulate the Antiviral Innate Immune Response in Porcine Intestinal Epitheliocytes
AU - Mizuno, Hiroya
AU - Tomotsune, Kae
AU - Islam, Md Aminul
AU - Funabashi, Ryutaro
AU - Albarracin, Leonardo
AU - Ikeda-Ohtsubo, Wakako
AU - Aso, Hisashi
AU - Takahashi, Hideki
AU - Kimura, Katsunori
AU - Villena, Julio
AU - Sasaki, Yasuko
AU - Kitazawa, Haruki
N1 - Funding Information:
YS, JV, and HK designed the study. HM, KT, RF, and MI performed the experiments. HM and LA performed the bioinformatic studies. JV, KK, HT, YS, and HK provided the financial support. JV, WI-O, HT, KK, YS, and HK contributed to data analysis and results interpretation. MI and JV wrote the manuscript. WI-O, HT, HA, KK, YS, and HK reviewed the manuscript. YS and HK approved the final version of the manuscript.
Funding Information:
Funding. This study was supported by a Grant-in-Aid for Scientific Research (A) (19H00965) and Open Partnership Joint Projects of JSPS Bilateral Joint Research Projects from the Japan Society for the Promotion of Science (JSPS) to HK. This research was supported by grants from the project of NARO Bio-oriented Technology Research Advancement Institution (research program on the development of innovative technology, No. 01002A) to HK, and the grants for ?Scientific Research on Innovative Areas? from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (Grant numbers: 16H06429, 16K21723, and 16H06435) to HT. This study was also supported by ANPCyT?FONCyT Grant PICT-2016-0410 to JV and by JSPS Core-to-Core Program, A. Advanced Research Networks entitled Establishment of international agricultural immunology research-core for a quantum improvement in food safety.
Publisher Copyright:
© Copyright © 2020 Mizuno, Tomotsune, Islam, Funabashi, Albarracin, Ikeda-Ohtsubo, Aso, Takahashi, Kimura, Villena, Sasaki and Kitazawa.
PY - 2020/5/19
Y1 - 2020/5/19
N2 - It was reported that exopolysaccharides (EPSs) from lactobacilli are able to differentially modulate mucosal antiviral immunity. Although research has described the ability of EPSs derived from Streptococcus thermophilus to modulate the mucosal immune system, their impact on antiviral immunity was less explored. In this work, we investigated the capacity of the EPS-producing S. thermophilus ST538 to modulate the innate antiviral immune response triggered by the activation of the Toll-like receptor 3 (TLR3) in porcine intestinal epitheliocytes (PIE cells). Moreover, in order to study the immunomodulatory potential of S. thermophilus ST538 EPS, we successfully developed two mutant strains through the knockout of the epsB or epsC genes. High-performance liquid chromatography and scanning electron microscopy studies demonstrated that the wild type (WT) strain produced as high as 595 μg/ml of EPS in the skim milk medium, while none of the mutant strains (S. thermophilus ΔepsB and ΔepsC) were able to produce EPS. Studies in PIE cells demonstrated that the EPS of S. thermophilus ST538 is able to significantly improve the expression of interferon β (IFN-β), interleukin 6 (IL-6), and C-X-C motif chemokine 10 (CXCL10) in response to TLR3 stimulation. The role of EPS in the modulation of antiviral immune response in PIE cells was confirmed by comparative studies of cell free culture supernatants and fermented skim milks obtained from S. thermophilus ΔepsB and ΔepsC. These results suggest that S. thermophilus ST538 could be used as an immunobiotic strain for the development of new immunologically functional foods, which might contribute to improve resistance against viral infections.
AB - It was reported that exopolysaccharides (EPSs) from lactobacilli are able to differentially modulate mucosal antiviral immunity. Although research has described the ability of EPSs derived from Streptococcus thermophilus to modulate the mucosal immune system, their impact on antiviral immunity was less explored. In this work, we investigated the capacity of the EPS-producing S. thermophilus ST538 to modulate the innate antiviral immune response triggered by the activation of the Toll-like receptor 3 (TLR3) in porcine intestinal epitheliocytes (PIE cells). Moreover, in order to study the immunomodulatory potential of S. thermophilus ST538 EPS, we successfully developed two mutant strains through the knockout of the epsB or epsC genes. High-performance liquid chromatography and scanning electron microscopy studies demonstrated that the wild type (WT) strain produced as high as 595 μg/ml of EPS in the skim milk medium, while none of the mutant strains (S. thermophilus ΔepsB and ΔepsC) were able to produce EPS. Studies in PIE cells demonstrated that the EPS of S. thermophilus ST538 is able to significantly improve the expression of interferon β (IFN-β), interleukin 6 (IL-6), and C-X-C motif chemokine 10 (CXCL10) in response to TLR3 stimulation. The role of EPS in the modulation of antiviral immune response in PIE cells was confirmed by comparative studies of cell free culture supernatants and fermented skim milks obtained from S. thermophilus ΔepsB and ΔepsC. These results suggest that S. thermophilus ST538 could be used as an immunobiotic strain for the development of new immunologically functional foods, which might contribute to improve resistance against viral infections.
KW - PIE cells
KW - Streptococcus thermophilus ST538
KW - antiviral immunity
KW - epsB
KW - epsC
KW - exopolysaccharides
KW - gene-knockout
UR - http://www.scopus.com/inward/record.url?scp=85085889903&partnerID=8YFLogxK
U2 - 10.3389/fmicb.2020.00894
DO - 10.3389/fmicb.2020.00894
M3 - Article
AN - SCOPUS:85085889903
VL - 11
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
SN - 1664-302X
M1 - 894
ER -