Lactobacilli Activate Human Dendritic Cells That Skew T Cells toward T Helper 1 Polarization

Professional antigen-presenting dendritic cells (DCs) are critical in regulating T cell immune responses at both systemic and mucosal sites. Many Lactobacillus species are normal members of the human gut microflora and most are regarded as safe when administered as probiotics. Because DCs can natura...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2005-02, Vol.102 (8), p.2880-2885
Main Authors: Mohamadzadeh, Mansour, Olson, Scott, Kalina, Warren V., Ruthel, Gordon, Demmin, Gretchen L., Warfield, Kelly L., Bavari, Sina, Klaenhammer, Todd R.
Format: Article
Language:English
Subjects:
Antigen presenting cells
Bacteria
Biological Sciences
Cell Polarity
Cytokines
Dendritic cells
Dendritic Cells - physiology
Epithelial cells
Escherichia coli
Homeostasis
Humans
Immunology
Interleukin-12 - biosynthesis
Interleukin-18 - biosynthesis
Lactobacillus
Lactobacillus - physiology
Lymphocyte Activation
Membrane Glycoproteins - genetics
Membrane Glycoproteins - physiology
Receptors, Cell Surface - genetics
Receptors, Cell Surface - physiology
Secretion
T lymphocytes
T-Lymphocytes - immunology
Th1 Cells - physiology
Toll-Like Receptors
Tumor Necrosis Factor-alpha - biosynthesis
Vaccines
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Summary:Professional antigen-presenting dendritic cells (DCs) are critical in regulating T cell immune responses at both systemic and mucosal sites. Many Lactobacillus species are normal members of the human gut microflora and most are regarded as safe when administered as probiotics. Because DCs can naturally or therapeutically encounter lactobacilli, we investigated the effects of several well defined strains, representing three species of Lactobacillus on human myeloid DCs (MDCs) and found that they modulated the phenotype and functions of human MDCs. Lactobacillus-exposed MDCs up-regulated HLA-DR, CD83, CD40, CD80, and CD86 and secreted high levels of IL-12 and IL-18, but not IL-10. IL-12 was sustained in MDCs exposed to all three Lactobacillus species in the presence of LPS from Escherichia coli, whereas LPS-induced IL-10 was greatly inhibited. MDCs activated with lactobacilli clearly skewed CD4+and CD8+T cells to T helper 1 and Tc1 polarization, as evidenced by secretion of IFN-γ, but not IL-4 or IL-13. These results emphasize a potentially important role for lactobacilli in modulating immunological functions of DCs and suggest that certain strains could be particularly advantageous as vaccine adjuvants, by promoting DCs to regulate T cell responses toward T helper 1 and Tc1 pathways.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0500098102