Gut commensal Limosilactobacillus reuteri induces atypical memory-like phenotype in human dendritic cells in vitro

Memory-like responses in innate immune cells confer nonspecific protection against secondary exposures. A number of microbial agents have been found to induce enhanced or diminished recall responses in innate cells, however, studies investigating the ability of probiotic bacteria to trigger such eff...

Full description

Saved in:
Bibliographic Details
Main Authors: Gintare Lasaviciute, Myriam Barz, Marieke van der Heiden, Claudia Arasa, Kanwal Tariq, Jaclyn Quin, Ann-Kristin Östlund Farrants, Eva Sverremark-Ekström
Format: Article
Language:English
Published: Taylor & Francis Group 2022-12-01
Series:Gut Microbes
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/19490976.2022.2045046
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850109183149473792
author Gintare Lasaviciute
Myriam Barz
Marieke van der Heiden
Claudia Arasa
Kanwal Tariq
Jaclyn Quin
Ann-Kristin Östlund Farrants
Eva Sverremark-Ekström
author_facet Gintare Lasaviciute
Myriam Barz
Marieke van der Heiden
Claudia Arasa
Kanwal Tariq
Jaclyn Quin
Ann-Kristin Östlund Farrants
Eva Sverremark-Ekström
author_sort Gintare Lasaviciute
collection DOAJ
description Memory-like responses in innate immune cells confer nonspecific protection against secondary exposures. A number of microbial agents have been found to induce enhanced or diminished recall responses in innate cells, however, studies investigating the ability of probiotic bacteria to trigger such effects are lacking. Here, we show that priming of human monocytes with a secretome from the gut probiotic bacterium Limosilactobacillus (L.) reuteri induces a mixed secondary response phenotype in monocyte-derived dendritic cells (mo-DCs), with a strong IL-6 and IL-1β response but low TNFα, IL-23 and IL-27 secretion. Instead, blood DC priming with L. reuteri-secretome resembles a tolerant state upon secondary exposure. A similar pattern was found in conventional and gut-like (retinoic acid exposed) DCs, although retinoic acid hampered TNFα and IL-6 production and enrichment of histone modifications in L. reuteri-secretome primed mo-DC cultures. Further, we show that the memory-like phenotype of mo-DCs, induced by priming stimuli, is important for subsequent T helper (Th) cell differentiation pathways and might determine the inflammatory nature of Th cells. We also show enhanced recall responses characterized by robust inflammatory cytokines and lactate production in the gut-like mo-DCs derived from β-glucan primed monocytes. Such responses were accompanied with enriched histone modifications at the promoter of genes associated with a trained phenotype in myeloid cells. Altogether, we demonstrate that a gut commensal-derived secretome prompts recall responses in human DCs which differ from that induced by classical training agents such as β-glucan. Our results could be beneficial for future therapeutic interventions where T cell responses are needed to be modulated.
format Article
id doaj-art-ce3c1d59cc6347eebb7d495674185fd4
institution OA Journals
issn 1949-0976
1949-0984
language English
publishDate 2022-12-01
publisher Taylor & Francis Group
record_format Article
series Gut Microbes
spelling doaj-art-ce3c1d59cc6347eebb7d495674185fd42025-08-20T02:38:10ZengTaylor & Francis GroupGut Microbes1949-09761949-09842022-12-0114110.1080/19490976.2022.2045046Gut commensal Limosilactobacillus reuteri induces atypical memory-like phenotype in human dendritic cells in vitroGintare Lasaviciute0Myriam Barz1Marieke van der Heiden2Claudia Arasa3Kanwal Tariq4Jaclyn Quin5Ann-Kristin Östlund Farrants6Eva Sverremark-Ekström7Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, SwedenDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, SwedenDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, SwedenDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, SwedenDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, SwedenCentral European Institute of Technology, Masaryk University, Brno, Czech RepublicDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, SwedenDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, SwedenMemory-like responses in innate immune cells confer nonspecific protection against secondary exposures. A number of microbial agents have been found to induce enhanced or diminished recall responses in innate cells, however, studies investigating the ability of probiotic bacteria to trigger such effects are lacking. Here, we show that priming of human monocytes with a secretome from the gut probiotic bacterium Limosilactobacillus (L.) reuteri induces a mixed secondary response phenotype in monocyte-derived dendritic cells (mo-DCs), with a strong IL-6 and IL-1β response but low TNFα, IL-23 and IL-27 secretion. Instead, blood DC priming with L. reuteri-secretome resembles a tolerant state upon secondary exposure. A similar pattern was found in conventional and gut-like (retinoic acid exposed) DCs, although retinoic acid hampered TNFα and IL-6 production and enrichment of histone modifications in L. reuteri-secretome primed mo-DC cultures. Further, we show that the memory-like phenotype of mo-DCs, induced by priming stimuli, is important for subsequent T helper (Th) cell differentiation pathways and might determine the inflammatory nature of Th cells. We also show enhanced recall responses characterized by robust inflammatory cytokines and lactate production in the gut-like mo-DCs derived from β-glucan primed monocytes. Such responses were accompanied with enriched histone modifications at the promoter of genes associated with a trained phenotype in myeloid cells. Altogether, we demonstrate that a gut commensal-derived secretome prompts recall responses in human DCs which differ from that induced by classical training agents such as β-glucan. Our results could be beneficial for future therapeutic interventions where T cell responses are needed to be modulated.https://www.tandfonline.com/doi/10.1080/19490976.2022.2045046Limosilactobacillus reuteridendritic cellsT helper cellsinnate immune memoryepigenetics
spellingShingle Gintare Lasaviciute
Myriam Barz
Marieke van der Heiden
Claudia Arasa
Kanwal Tariq
Jaclyn Quin
Ann-Kristin Östlund Farrants
Eva Sverremark-Ekström
Gut commensal Limosilactobacillus reuteri induces atypical memory-like phenotype in human dendritic cells in vitro
Gut Microbes
Limosilactobacillus reuteri
dendritic cells
T helper cells
innate immune memory
epigenetics
title Gut commensal Limosilactobacillus reuteri induces atypical memory-like phenotype in human dendritic cells in vitro
title_full Gut commensal Limosilactobacillus reuteri induces atypical memory-like phenotype in human dendritic cells in vitro
title_fullStr Gut commensal Limosilactobacillus reuteri induces atypical memory-like phenotype in human dendritic cells in vitro
title_full_unstemmed Gut commensal Limosilactobacillus reuteri induces atypical memory-like phenotype in human dendritic cells in vitro
title_short Gut commensal Limosilactobacillus reuteri induces atypical memory-like phenotype in human dendritic cells in vitro
title_sort gut commensal limosilactobacillus reuteri induces atypical memory like phenotype in human dendritic cells in vitro
topic Limosilactobacillus reuteri
dendritic cells
T helper cells
innate immune memory
epigenetics
url https://www.tandfonline.com/doi/10.1080/19490976.2022.2045046
work_keys_str_mv AT gintarelasaviciute gutcommensallimosilactobacillusreuteriinducesatypicalmemorylikephenotypeinhumandendriticcellsinvitro
AT myriambarz gutcommensallimosilactobacillusreuteriinducesatypicalmemorylikephenotypeinhumandendriticcellsinvitro
AT mariekevanderheiden gutcommensallimosilactobacillusreuteriinducesatypicalmemorylikephenotypeinhumandendriticcellsinvitro
AT claudiaarasa gutcommensallimosilactobacillusreuteriinducesatypicalmemorylikephenotypeinhumandendriticcellsinvitro
AT kanwaltariq gutcommensallimosilactobacillusreuteriinducesatypicalmemorylikephenotypeinhumandendriticcellsinvitro
AT jaclynquin gutcommensallimosilactobacillusreuteriinducesatypicalmemorylikephenotypeinhumandendriticcellsinvitro
AT annkristinostlundfarrants gutcommensallimosilactobacillusreuteriinducesatypicalmemorylikephenotypeinhumandendriticcellsinvitro
AT evasverremarkekstrom gutcommensallimosilactobacillusreuteriinducesatypicalmemorylikephenotypeinhumandendriticcellsinvitro