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.
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.
Smits
Hermelijn H
HH
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Engering
Anneke
A
van der Kleij
Desiree
D
de Jong
Esther C
EC
Schipper
Kim
K
van Capel
Toni M M
TM
Zaat
Bas A J
BA
Yazdanbakhsh
Maria
M
Wierenga
Eddy A
EA
van Kooyk
Yvette
Y
Kapsenberg
Martien L
ML
D015703:Antigens, CD / Q000276:immunology*; D015815:Cell Adhesion Molecules; D002455:Cell Division; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000494:pharmacology; D007778:Lactobacillus; D007780:Lacticaseibacillus casei; D037181:Lectins, C-Type / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D019936:Probiotics; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C483616:ICAM3 protein, human; D037181:Lectins, C-Type; D016753:Interleukin-10