TY - JOUR
T1 - Genomic characterization of Lactobacillus delbrueckii TUA4408L and evaluation of the antiviral activities of its extracellular polysaccharides in porcine intestinal epithelial cells
AU - Kanmani, Paulraj
AU - Albarracin, Leonardo
AU - Kobayashi, Hisakazu
AU - Hebert, Elvira Maria
AU - Saavedra, Lucila
AU - Komatsu, Ryoya
AU - Gatica, Brian
AU - Miyazaki, Ayako
AU - Ikeda-Ohtsubo, Wakako
AU - Suda, Yoshihito
AU - Aso, Hisashi
AU - Egusa, Shintaro
AU - Mishima, Takashi
AU - Salas-Burgos, Alexis
AU - Takahashi, Hideki
AU - Villena, Julio
AU - Kitazawa, Haruki
N1 - Funding Information:
This study was supported by a Grant-in-Aid for Scientific Research (B)(2) (24380146, 16H05019), Challenging Exploratory Research (23658216, 26660216, 16K15028), and Open Partnership Joint Projects of JSPS Bilateral Joint Research Projects from the Japan Society for the Promotion of Science (JSPS) to HaK. PK was supported by JSPS (Postdoctoral Fellowship for Foreign Researchers, Program No. 25-03397 and 15F15401, respectively). This work was supported 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. This study was also financially supported by grants for Scientific Research on Innovative Areas from the Ministry of Education, Culture, Science, Sports, and Technology (MEXT) of Japan (Grant numbers: 16H06429, 16K21723, and 16H06435).
Publisher Copyright:
© 2007 - 2018 Frontiers Media S.A. All Rights Reserved.
PY - 2018/9/24
Y1 - 2018/9/24
N2 - In lactic acid bacteria, the synthesis of exopolysaccharides (EPS) has been associated with some favorable technological properties as well as health-promoting benefits. Research works have shown the potential of EPS produced by lactobacilli to differentially modulate immune responses. However, most studies were performed in immune cells and few works have concentrated in the immunomodulatory activities of EPS in non-immune cells such as intestinal epithelial cells. In addition, the cellular and molecular mechanisms involved in the immunoregulatory effects of EPS have not been studied in detail. In this work, we have performed a genomic characterization of Lactobacillus delbrueckii subsp. delbrueckii TUA4408L and evaluated the immunomodulatory and antiviral properties of its acidic (APS) and neutral (NPS) EPS in porcine intestinal epithelial (PIE) cells. Whole genome sequencing allowed the analysis of the general features of L. delbrueckii TUA4408L genome as well as the characterization of its EPS genes. A typical EPS gene cluster was found in the TUA4408L genome consisting in five highly conserved genes epsA-E, and a variable region, which includes the genes for the polymerase wzy, the flippase wzx, and seven glycosyltransferases. In addition, we demonstrated here for the first time that L. delbrueckii TUA4408L and its EPS are able to improve the resistance of PIE cells against rotavirus infection by reducing viral replication and regulating inflammatory response. Moreover, studies in PIE cells demonstrated that the TUA4408L strain and its EPS differentially modulate the antiviral innate immune response triggered by the activation of Toll-like receptor 3 (TLR3). L. delbrueckii TUA4408L and its EPS are capable of increasing the activation of interferon regulatory factor (IRF)-3 and nuclear factor κB (NF-κB) signaling pathways leading to an improved expression of the antiviral factors interferon (IFN)-β, Myxovirus resistance gene A (MxA) and RNaseL.
AB - In lactic acid bacteria, the synthesis of exopolysaccharides (EPS) has been associated with some favorable technological properties as well as health-promoting benefits. Research works have shown the potential of EPS produced by lactobacilli to differentially modulate immune responses. However, most studies were performed in immune cells and few works have concentrated in the immunomodulatory activities of EPS in non-immune cells such as intestinal epithelial cells. In addition, the cellular and molecular mechanisms involved in the immunoregulatory effects of EPS have not been studied in detail. In this work, we have performed a genomic characterization of Lactobacillus delbrueckii subsp. delbrueckii TUA4408L and evaluated the immunomodulatory and antiviral properties of its acidic (APS) and neutral (NPS) EPS in porcine intestinal epithelial (PIE) cells. Whole genome sequencing allowed the analysis of the general features of L. delbrueckii TUA4408L genome as well as the characterization of its EPS genes. A typical EPS gene cluster was found in the TUA4408L genome consisting in five highly conserved genes epsA-E, and a variable region, which includes the genes for the polymerase wzy, the flippase wzx, and seven glycosyltransferases. In addition, we demonstrated here for the first time that L. delbrueckii TUA4408L and its EPS are able to improve the resistance of PIE cells against rotavirus infection by reducing viral replication and regulating inflammatory response. Moreover, studies in PIE cells demonstrated that the TUA4408L strain and its EPS differentially modulate the antiviral innate immune response triggered by the activation of Toll-like receptor 3 (TLR3). L. delbrueckii TUA4408L and its EPS are capable of increasing the activation of interferon regulatory factor (IRF)-3 and nuclear factor κB (NF-κB) signaling pathways leading to an improved expression of the antiviral factors interferon (IFN)-β, Myxovirus resistance gene A (MxA) and RNaseL.
KW - Antiviral activity
KW - Genome sequence
KW - Immunobiotics
KW - Lactobacillus delbrueckii TUA4408L
KW - Porcine intestinal epithelial cells
KW - Rotavirus
KW - TLR3
UR - http://www.scopus.com/inward/record.url?scp=85054893277&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85054893277&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2018.02178
DO - 10.3389/fimmu.2018.02178
M3 - Article
C2 - 30319634
AN - SCOPUS:85054893277
SN - 1664-3224
VL - 9
JO - Frontiers in Immunology
JF - Frontiers in Immunology
IS - SEP
M1 - 2178
ER -