title: The impact of Lactobacillus plantarum WCFS1 teichoic acid D-alanylation on the generation of effector and regulatory T-cells in healthy mice.
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.
authors: Top Institute Food and Nutrition, Wageningen, The Netherlands.
authors: Maaike J
authors: MJ
authors: Smelt
authors: Bart J
authors: BJ
authors: de Haan
authors: Peter A
authors: PA
authors: Bron
authors: Iris
authors: I
authors: van Swam
authors: Marjolein
authors: M
authors: Meijerink
authors: Jerry M
authors: JM
authors: Wells
authors: Michiel
authors: M
authors: Kleerebezem
authors: Marijke M
authors: MM
authors: Faas
authors: Paul
authors: P
authors: de Vos
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002473:Cell Wall / Q000737:chemistry / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D056747:Immunomodulation; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D048191:Lactiplantibacillus plantarum / Q000737:chemistry / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D008643:Mesentery; D051379:Mice; D010581:Peyer's Patches / Q000276:immunology / Q000378:metabolism; D019936:Probiotics; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D013682:Teichoic Acids / Q000276:immunology* / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; C026244:alanyl-lipoteichoic acid
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