The impact of Lactobacillus plantarum WCFS1 teichoic acid D-alanylation on the generation of effector and regulatory T-cells in healthy mice

Maaike J Smelt, Bart J de Haan, Peter A Bron, Iris van Swam, Marjolein Meijerink, Jerry M Wells, Michiel Kleerebezem, Marijke M Faas, Paul de Vos

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

To date it remains unclear how probiotics affect the immune system. Bacterial envelope components may play an essential role, as these are the first to establish bacterial-host cell interactions. Teichoic acids (TAs), and especially lipoteichoic acids, are the most pro-inflammatory components of the gram-positive bacterial envelope. This effect is dependent on D-alanyl substitution of the TA backbone and interactions with TLR2 on host cells. Although the pro-inflammatory properties of TAs have been established in vitro, it remains unclear how TAs affect immunomodulation in vivo. In this study, we investigated the role of TA D-alanylation on L. plantarum-induced intestinal and systemic immunomodulation in vivo. For this, we compared the effect of L. plantarum WCFS1 and its TA D-Alanylation negative derivative (dltX-D) on the distribution of dendritic cell and T cell populations and responses in healthy mice. We demonstrated that the majority of the L. plantarum-induced in vivo immunomodulatory effects were dependent on D-alanylation (D-Ala), as some L. plantarum WCFS1-induced immune changes were not observed in the dltX-D-treated group and some were only observed after treatment with dltX-D. Strikingly, not only pro-inflammatory immune responses were abolished in the absence of D-Ala substitution, but also anti-inflammatory responses, such as the L. plantarum-induced generation of regulatory T cells in the spleen. With this study we provide insight in host-microbe interactions, by demonstrating the involvement of D-alanylation of TAs on the bacterial membrane in intestinal and systemic immunomodulation in healthy mice. © 2013 Smelt et al.
Original languageEnglish
Pages (from-to)e63099
JournalPLOS one
Volume8
Issue number4
DOIs
Publication statusPublished - 30 Apr 2013
Externally publishedYes

Fingerprint

Teichoic Acids
Lactobacillus plantarum
T-cells
Regulatory T-Lymphocytes
T-lymphocytes
mice
immunomodulation
Immunomodulation
Substitution reactions
Immune system
Probiotics
dendritic cells
teichoic acids
Cell Communication
Dendritic Cells
probiotics
immune system
Immune System
spleen
Anti-Inflammatory Agents

Keywords

  • Animals
  • CD4-Positive T-Lymphocytes/immunology
  • CD8-Positive T-Lymphocytes/immunology
  • Cell Line
  • Cell Wall/chemistry
  • Cytokines/immunology
  • Dendritic Cells/immunology
  • Forkhead Transcription Factors/metabolism
  • Humans
  • Immunomodulation
  • Inflammation/immunology
  • Interleukin-2 Receptor alpha Subunit/metabolism
  • Intestinal Mucosa/immunology
  • Lactobacillus plantarum/chemistry
  • Lymph Nodes/immunology
  • Male
  • Mesentery
  • Mice
  • Peyer's Patches/immunology
  • Probiotics
  • Signal Transduction
  • Spleen/immunology
  • T-Lymphocyte Subsets/immunology
  • T-Lymphocytes, Regulatory/immunology
  • Teichoic Acids/immunology
  • Toll-Like Receptor 2/metabolism

Cite this

Smelt, Maaike J ; de Haan, Bart J ; Bron, Peter A ; van Swam, Iris ; Meijerink, Marjolein ; Wells, Jerry M ; Kleerebezem, Michiel ; Faas, Marijke M ; de Vos, Paul. / The impact of Lactobacillus plantarum WCFS1 teichoic acid D-alanylation on the generation of effector and regulatory T-cells in healthy mice. In: PLOS one. 2013 ; Vol. 8, No. 4. pp. e63099.
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abstract = "To date it remains unclear how probiotics affect the immune system. Bacterial envelope components may play an essential role, as these are the first to establish bacterial-host cell interactions. Teichoic acids (TAs), and especially lipoteichoic acids, are the most pro-inflammatory components of the gram-positive bacterial envelope. This effect is dependent on D-alanyl substitution of the TA backbone and interactions with TLR2 on host cells. Although the pro-inflammatory properties of TAs have been established in vitro, it remains unclear how TAs affect immunomodulation in vivo. In this study, we investigated the role of TA D-alanylation on L. plantarum-induced intestinal and systemic immunomodulation in vivo. For this, we compared the effect of L. plantarum WCFS1 and its TA D-Alanylation negative derivative (dltX-D) on the distribution of dendritic cell and T cell populations and responses in healthy mice. We demonstrated that the majority of the L. plantarum-induced in vivo immunomodulatory effects were dependent on D-alanylation (D-Ala), as some L. plantarum WCFS1-induced immune changes were not observed in the dltX-D-treated group and some were only observed after treatment with dltX-D. Strikingly, not only pro-inflammatory immune responses were abolished in the absence of D-Ala substitution, but also anti-inflammatory responses, such as the L. plantarum-induced generation of regulatory T cells in the spleen. With this study we provide insight in host-microbe interactions, by demonstrating the involvement of D-alanylation of TAs on the bacterial membrane in intestinal and systemic immunomodulation in healthy mice. {\circledC} 2013 Smelt et al.",
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author = "Smelt, {Maaike J} and {de Haan}, {Bart J} and Bron, {Peter A} and {van Swam}, Iris and Marjolein Meijerink and Wells, {Jerry M} and Michiel Kleerebezem and Faas, {Marijke M} and {de Vos}, Paul",
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month = "4",
day = "30",
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Smelt, MJ, de Haan, BJ, Bron, PA, van Swam, I, Meijerink, M, Wells, JM, Kleerebezem, M, Faas, MM & de Vos, P 2013, 'The impact of Lactobacillus plantarum WCFS1 teichoic acid D-alanylation on the generation of effector and regulatory T-cells in healthy mice', PLOS one, vol. 8, no. 4, pp. e63099. https://doi.org/10.1371/journal.pone.0063099

The impact of Lactobacillus plantarum WCFS1 teichoic acid D-alanylation on the generation of effector and regulatory T-cells in healthy mice. / Smelt, Maaike J; de Haan, Bart J; Bron, Peter A; van Swam, Iris; Meijerink, Marjolein; Wells, Jerry M; Kleerebezem, Michiel; Faas, Marijke M; de Vos, Paul.

In: PLOS one, Vol. 8, No. 4, 30.04.2013, p. e63099.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - The impact of Lactobacillus plantarum WCFS1 teichoic acid D-alanylation on the generation of effector and regulatory T-cells in healthy mice

AU - Smelt, Maaike J

AU - de Haan, Bart J

AU - Bron, Peter A

AU - van Swam, Iris

AU - Meijerink, Marjolein

AU - Wells, Jerry M

AU - Kleerebezem, Michiel

AU - Faas, Marijke M

AU - de Vos, Paul

PY - 2013/4/30

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N2 - To date it remains unclear how probiotics affect the immune system. Bacterial envelope components may play an essential role, as these are the first to establish bacterial-host cell interactions. Teichoic acids (TAs), and especially lipoteichoic acids, are the most pro-inflammatory components of the gram-positive bacterial envelope. This effect is dependent on D-alanyl substitution of the TA backbone and interactions with TLR2 on host cells. Although the pro-inflammatory properties of TAs have been established in vitro, it remains unclear how TAs affect immunomodulation in vivo. In this study, we investigated the role of TA D-alanylation on L. plantarum-induced intestinal and systemic immunomodulation in vivo. For this, we compared the effect of L. plantarum WCFS1 and its TA D-Alanylation negative derivative (dltX-D) on the distribution of dendritic cell and T cell populations and responses in healthy mice. We demonstrated that the majority of the L. plantarum-induced in vivo immunomodulatory effects were dependent on D-alanylation (D-Ala), as some L. plantarum WCFS1-induced immune changes were not observed in the dltX-D-treated group and some were only observed after treatment with dltX-D. Strikingly, not only pro-inflammatory immune responses were abolished in the absence of D-Ala substitution, but also anti-inflammatory responses, such as the L. plantarum-induced generation of regulatory T cells in the spleen. With this study we provide insight in host-microbe interactions, by demonstrating the involvement of D-alanylation of TAs on the bacterial membrane in intestinal and systemic immunomodulation in healthy mice. © 2013 Smelt et al.

AB - To date it remains unclear how probiotics affect the immune system. Bacterial envelope components may play an essential role, as these are the first to establish bacterial-host cell interactions. Teichoic acids (TAs), and especially lipoteichoic acids, are the most pro-inflammatory components of the gram-positive bacterial envelope. This effect is dependent on D-alanyl substitution of the TA backbone and interactions with TLR2 on host cells. Although the pro-inflammatory properties of TAs have been established in vitro, it remains unclear how TAs affect immunomodulation in vivo. In this study, we investigated the role of TA D-alanylation on L. plantarum-induced intestinal and systemic immunomodulation in vivo. For this, we compared the effect of L. plantarum WCFS1 and its TA D-Alanylation negative derivative (dltX-D) on the distribution of dendritic cell and T cell populations and responses in healthy mice. We demonstrated that the majority of the L. plantarum-induced in vivo immunomodulatory effects were dependent on D-alanylation (D-Ala), as some L. plantarum WCFS1-induced immune changes were not observed in the dltX-D-treated group and some were only observed after treatment with dltX-D. Strikingly, not only pro-inflammatory immune responses were abolished in the absence of D-Ala substitution, but also anti-inflammatory responses, such as the L. plantarum-induced generation of regulatory T cells in the spleen. With this study we provide insight in host-microbe interactions, by demonstrating the involvement of D-alanylation of TAs on the bacterial membrane in intestinal and systemic immunomodulation in healthy mice. © 2013 Smelt et al.

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KW - CD4-Positive T-Lymphocytes/immunology

KW - CD8-Positive T-Lymphocytes/immunology

KW - Cell Line

KW - Cell Wall/chemistry

KW - Cytokines/immunology

KW - Dendritic Cells/immunology

KW - Forkhead Transcription Factors/metabolism

KW - Humans

KW - Immunomodulation

KW - Inflammation/immunology

KW - Interleukin-2 Receptor alpha Subunit/metabolism

KW - Intestinal Mucosa/immunology

KW - Lactobacillus plantarum/chemistry

KW - Lymph Nodes/immunology

KW - Male

KW - Mesentery

KW - Mice

KW - Peyer's Patches/immunology

KW - Probiotics

KW - Signal Transduction

KW - Spleen/immunology

KW - T-Lymphocyte Subsets/immunology

KW - T-Lymphocytes, Regulatory/immunology

KW - Teichoic Acids/immunology

KW - Toll-Like Receptor 2/metabolism

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