TY - JOUR
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
Y1 - 2013/4/30
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.
KW - Animals
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
KW - probiotica
UR - http://www.mendeley.com/research/impact-lactobacillus-plantarum-wcfs1-teichoic-acid-dalanylation-generation-effector-regulatory-tcell
U2 - 10.1371/journal.pone.0063099
DO - 10.1371/journal.pone.0063099
M3 - Article
C2 - 23646181
SN - 1932-6203
VL - 8
JO - PLoS ONE
JF - PLoS ONE
IS - 4
ER -