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


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
JournalPLoS ONE
Issue number4
Publication statusPublished - 30 Apr 2013
Externally publishedYes


  • 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


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