Selective probiotic bacteria induce IL-10-producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin

Hermelijn H Smits, Anneke Engering, Desiree van der Kleij, Esther C de Jong, Kim Schipper, Toni M M van Capel, Bas A J Zaat, Maria Yazdanbakhsh, Eddy A Wierenga, Yvette van Kooyk, Martien L Kapsenberg

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: Lactobacilli are probiotic bacteria that are frequently tested in the management of allergic diseases or gastroenteritis. It is hypothesized that these probiotics have immunoregulatory properties and promote mucosal tolerance, which is in part mediated by regulatory T cells (Treg cells). On the basis of pathogenic or tissue-specific priming, dendritic cells (DC) acquire different T cell-instructive signals and drive the differentiation of naive T H cells into either T H 1, T H 2, or regulatory effector T cells.

OBJECTIVE: We studied in what way different species of lactobacilli prime human DCs for their ability to drive Treg cells.

METHODS: Human monocyte-derived DCs were cultured in vitro with lactobacilli of different species.

RESULTS: Two different species of lactobacilli, Lactobacillus reuteri and Lactobacillus casei , but not Lactobacillus plantarum, prime monocyte-derived DCs to drive the development of Treg cells. These Treg cells produced increased levels of IL-10 and were capable of inhibiting the proliferation of bystander T cells in an IL-10-dependent fashion. Strikingly, both L reuteri and L casei , but not L plantarum , bind the C-type lectin DC-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN). Blocking antibodies to DC-SIGN inhibited the induction of the Treg cells by these probiotic bacteria, stressing that ligation of DC-SIGN can actively prime DCs to induce Treg cells.

CONCLUSIONS: The targeting of DC-SIGN by certain probiotic bacteria might explain their beneficial effect in the treatment of a number of inflammatory diseases, including atopic dermatitis and Crohn's disease.

Original languageEnglish
Pages (from-to)1260-1267
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume115
Issue number6
DOIs
Publication statusPublished - Jun 2005

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