TY - JOUR
T1 - Ligilactobacillus salivarius Strains Isolated From the Porcine Gut Modulate Innate Immune Responses in Epithelial Cells and Improve Protection Against Intestinal Viral-Bacterial Superinfection
AU - Indo, Yuhki
AU - Kitahara, Shugo
AU - Tomokiyo, Mikado
AU - Araki, Shota
AU - Islam, Md Aminul
AU - Zhou, Binghui
AU - Albarracin, Leonardo
AU - Miyazaki, Ayako
AU - Ikeda-Ohtsubo, Wakako
AU - Nochi, Tomonori
AU - Takenouchi, Takato
AU - Uenishi, Hirohide
AU - Aso, Hisashi
AU - Takahashi, Hideki
AU - Kurata, Shoichiro
AU - Villena, Julio
AU - Kitazawa, Haruki
N1 - Funding Information:
This study 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), by a Grant-in-Aid for Scientific Research (A) (19H00965) from the Japan Society for the Promotion of Science (JSPS), by Japan Racing Association (JRA) Livestock Industry Promotion Project, and by the Association for Research on Lactic Acid Bacteria to HK. This study was also supported by ANPCyT– FONCyT Grant PICT-2016-0410 to JV, and by Tohoku University Research Program “Frontier Research in Duo” (FRiD) to SK. This work was also supported by grants for Scientific Research on Innovative Areas from the Ministry of Education, Culture, Science, Sports, and Technology (MEXT) of Japan (16H06429, 16K21723, and 16H06435) and Grant-in-Aid for Challenging Research (Exploratory, 19K22300) to HT, 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, and by AMED Grant Number JP21zf0127001. MAI was supported by JSPS (Postdoctoral Fellowship for Foreign Researchers, Program No. 18F18081). M.T. was supported by Tohoku University Global Hagi Scholarship.
Publisher Copyright:
© Copyright © 2021 Indo, Kitahara, Tomokiyo, Araki, Islam, Zhou, Albarracin, Miyazaki, Ikeda-Ohtsubo, Nochi, Takenouchi, Uenishi, Aso, Takahashi, Kurata, Villena and Kitazawa.
PY - 2021/6/7
Y1 - 2021/6/7
N2 - Previously, we constructed a library of Ligilactobacillus salivarius strains from the intestine of wakame-fed pigs and reported a strain-dependent capacity to modulate IFN-β expression in porcine intestinal epithelial (PIE) cells. In this work, we further characterized the immunomodulatory activities of L. salivarius strains from wakame-fed pigs by evaluating their ability to modulate TLR3- and TLR4-mediated innate immune responses in PIE cells. Two strains with a remarkable immunomodulatory potential were selected: L. salivarius FFIG35 and FFIG58. Both strains improved IFN-β, IFN-λ and antiviral factors expression in PIE cells after TLR3 activation, which correlated with an enhanced resistance to rotavirus infection. Moreover, a model of enterotoxigenic E. coli (ETEC)/rotavirus superinfection in PIE cells was developed. Cells were more susceptible to rotavirus infection when the challenge occurred in conjunction with ETEC compared to the virus alone. However, L. salivarius FFIG35 and FFIG58 maintained their ability to enhance IFN-β, IFN-λ and antiviral factors expression in PIE cells, and to reduce rotavirus replication in the context of superinfection. We also demonstrated that FFIG35 and FFIG58 strains regulated the immune response of PIE cells to rotavirus challenge or ETEC/rotavirus superinfection through the modulation of negative regulators of the TLR signaling pathway. In vivo studies performed in mice models confirmed the ability of L. salivarius FFIG58 to beneficially modulate the innate immune response and protect against ETEC infection. The results of this work contribute to the understanding of beneficial lactobacilli interactions with epithelial cells and allow us to hypothesize that the FFIG35 or FFIG58 strains could be used for the development of highly efficient functional feed to improve immune health status and reduce the severity of intestinal infections and superinfections in weaned piglets.
AB - Previously, we constructed a library of Ligilactobacillus salivarius strains from the intestine of wakame-fed pigs and reported a strain-dependent capacity to modulate IFN-β expression in porcine intestinal epithelial (PIE) cells. In this work, we further characterized the immunomodulatory activities of L. salivarius strains from wakame-fed pigs by evaluating their ability to modulate TLR3- and TLR4-mediated innate immune responses in PIE cells. Two strains with a remarkable immunomodulatory potential were selected: L. salivarius FFIG35 and FFIG58. Both strains improved IFN-β, IFN-λ and antiviral factors expression in PIE cells after TLR3 activation, which correlated with an enhanced resistance to rotavirus infection. Moreover, a model of enterotoxigenic E. coli (ETEC)/rotavirus superinfection in PIE cells was developed. Cells were more susceptible to rotavirus infection when the challenge occurred in conjunction with ETEC compared to the virus alone. However, L. salivarius FFIG35 and FFIG58 maintained their ability to enhance IFN-β, IFN-λ and antiviral factors expression in PIE cells, and to reduce rotavirus replication in the context of superinfection. We also demonstrated that FFIG35 and FFIG58 strains regulated the immune response of PIE cells to rotavirus challenge or ETEC/rotavirus superinfection through the modulation of negative regulators of the TLR signaling pathway. In vivo studies performed in mice models confirmed the ability of L. salivarius FFIG58 to beneficially modulate the innate immune response and protect against ETEC infection. The results of this work contribute to the understanding of beneficial lactobacilli interactions with epithelial cells and allow us to hypothesize that the FFIG35 or FFIG58 strains could be used for the development of highly efficient functional feed to improve immune health status and reduce the severity of intestinal infections and superinfections in weaned piglets.
KW - innate immunity
KW - intestinal superinfection
KW - lactobacilli
KW - porcine intestinal epithelial cells
KW - rotavirus infection
UR - http://www.scopus.com/inward/record.url?scp=85108353678&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85108353678&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2021.652923
DO - 10.3389/fimmu.2021.652923
M3 - Article
C2 - 34163470
AN - SCOPUS:85108353678
VL - 12
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
M1 - 652923
ER -