Live biotherapeutic products constitute an emerging therapeutic approach to prevent or treat inflammatory bowel diseases. Lactobacillus acidophilus is a constituent of the human microbiota with probiotic potential, that is illustrated by improvement of intestinal inflammation and antimicrobial activity against several pathogens. In this study, we evaluated the immunomodulatory properties of the L. acidophilus strain BIO5768 at steady state and upon acute inflammation. Supplementation of naïve mice with BIO5768 heightened the transcript level of some IL-17 target genes encoding for protein with microbicidal activity independently of NOD2 signaling. Of these, the BIO5768-induced expression of Angiogenin-4 was blunted in monocolonized mice that are deficient for the receptor of IL-17 (but not for NOD2). Interestingly, priming of bone marrow derived dendritic cells by BIO5768 enhanced their ability to support the secretion of IL-17 by CD4+ T cells. Equally of importance, the production of IL-22 by type 3 innate lymphoid cells is concomitantly heightened in response to BIO5768. When administered alone or in combination with Bifidobacterium animalis spp. lactis BIO5764 and Limosilactobacillus reuteri, BIO5768 was able to alleviate at least partially intestinal inflammation induced by Citrobacter rodentium infection. Furthermore, BIO5768 was also able to improve colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). In conclusion, we identify a new potential probiotic strain for the management of inflammatory bowel diseases, and provide some insights into its IL-17-dependent and independent mode of action.

Bioprox 7 rue Aristide Briand 92300 Levallois Perret France

Division of Immunology and South African Medical Research Council Immunology Department of Clinical Immunology Faculty of Health Sciences University of Cape Town Anzio Road Observatory 7925 Cape Town RSA

INEM UMR7355 Molecular Immunology Institute of Infectious Diseases and Molecular Medicine and Infectious Diseases University and CNRS Orléans France

Institute of Immunology and Microbiology 1st Faculty of Medicine Charles University Prague Czech Republic

Institute of Molecular Genetics Czech Centre for Phenogenomics Czech Academy of Sciences 252 50 Vestec Czech Republic

Research Group of Industrial Microbiology and Food Biotechnology Faculty of Sciences and Bioengineering Sciences Vrije Universiteit Brussel Brussels Belgium

Univ Lille CNRS Inserm CHU Lille Institut Pasteur de Lille U1019 UMR 9017 CIIL Centre d'Infection et d'Immunité de Lille 59000 Lille France

Univ Lille Inserm U1003 59000 Lille France

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