Ligilactobacillus salivarius Strains Isolated From the Porcine Gut Modulate Innate Immune Responses in Epithelial Cells and Improve Protection Against Intestinal Viral-Bacterial Superinfection
Open Access
- 7 June 2021
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Immunology
Abstract
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.Keywords
Funding Information
- Japan Society for the Promotion of Science
This publication has 76 references indexed in Scilit:
- Innate immune response to homologous rotavirus infection in the small intestinal villous epithelium at single-cell resolutionProceedings of the National Academy of Sciences of the United States of America, 2012
- Stimulation of macrophages by immunobiotic Lactobacillus strains: influence beyond the intestinal tractMicrobiology and Immunology, 2012
- Immunobiotic Lactobacillus jensenii Elicits Anti-Inflammatory Activity in Porcine Intestinal Epithelial Cells by Modulating Negative Regulators of the Toll-Like Receptor Signaling PathwayInfection and Immunity, 2012
- IFN-λ determines the intestinal epithelial antiviral host defenseProceedings of the National Academy of Sciences of the United States of America, 2011
- The Early Interferon Response to Rotavirus Is Regulated by PKR and Depends on MAVS/IPS-1, RIG-I, MDA-5, and IRF3Journal of Virology, 2011
- New Insights into the Role of RNase L in Innate ImmunityJournal of Interferon & Cytokine Research, 2011
- Protein Kinase R Is Responsible for the Phosphorylation of eIF2α in Rotavirus InfectionJournal of Virology, 2010
- The A20 Deubiquitinase Activity Negatively Regulates LMP1 Activation of IRF7Journal of Virology, 2010
- Variation in Antagonism of the Interferon Response to Rotavirus NSP1 Results in Differential Infectivity in Mouse Embryonic FibroblastsJournal of Virology, 2009
- Type III Interferon (IFN) Induces a Type I IFN-Like Response in a Restricted Subset of Cells through Signaling Pathways Involving both the Jak-STAT Pathway and the Mitogen-Activated Protein KinasesJournal of Virology, 2007