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 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-gamma, 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.
Mohamadzadeh
Mansour
M
National Cancer Institute, Frederick, MD 21702, USA. mzadeh@ncifcrf.gov
Olson
Scott
S
Kalina
Warren V
WV
Ruthel
Gordon
G
Demmin
Gretchen L
GL
Warfield
Kelly L
KL
Bavari
Sina
S
Klaenhammer
Todd R
TR
D016764:Cell Polarity; D003713:Dendritic Cells / Q000502:physiology*; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis; D020382:Interleukin-18 / Q000096:biosynthesis; D007778:Lactobacillus / Q000502:physiology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000502:physiology*; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D020382:Interleukin-18; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12