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Clinical and Vaccine Immunology, March 2006, p. 365-375, Vol. 13, No. 3
1071-412X/06/$08.00+0     doi:10.1128/CVI.13.3.365-375.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Lactic Acid Bacteria Inducing a Weak Interleukin-12 and Tumor Necrosis Factor Alpha Response in Human Dendritic Cells Inhibit Strongly Stimulating Lactic Acid Bacteria but Act Synergistically with Gram-Negative Bacteria

Louise Hjerrild Zeuthen,* Hanne Risager Christensen,{dagger} and Hanne Frøkiær

BioCentrum-DTU, Biochemistry and Nutrition Group, Technical University of Denmark, Kgs. Lyngby, Denmark

Received 4 October 2005/ Returned for modification 10 November 2005/ Accepted 25 November 2005

The development and maintenance of immune homeostasis indispensably depend on signals from the gut flora. Lactic acid bacteria (LAB), which are gram-positive (G+) organisms, are plausible significant players and have received much attention. Gram-negative (G–) commensals, such as members of the family Enterobacteriaceae, may, however, be immunomodulators that are as important as G+ organisms but tend to be overlooked. Dendritic cells (DCs) are crucial immune regulators, and therefore, the present study aimed at investigating differences among human gut flora-derived LAB and G– bacteria in their patterns of DC polarization. Human monocyte-derived DCs were exposed to UV-killed bacteria, and cytokine secretion and surface marker expression were analyzed. Profound differences in the DC polarization patterns were found among the strains. While strains of LAB varied greatly in their capacity to induce interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-{alpha}), G– strains were consistently weak IL-12 and TNF-{alpha} inducers. All strains induced significant amounts of IL-10, but G– bacteria were far more potent IL-10 inducers than LAB. Interestingly, we found that when weakly IL-12- and TNF-{alpha}-inducing LAB and strong IL-12- and TNF-{alpha}-inducing LAB were mixed, the weakly IL-12- and TNF-{alpha}-inducing LAB efficiently inhibited otherwise strong IL-12- and TNF-{alpha}-inducing LAB, yet when weakly IL-12- and TNF-{alpha}-inducing LAB were mixed with G– bacteria, they synergistically induced IL-12 and TNF-{alpha}. Furthermore, strong IL-12- and TNF-{alpha}-inducing LAB efficiently up-regulated surface markers (CD40, CD83, CD86, and HLA-DR), which were inhibited by weakly IL-12- and TNF-{alpha}-inducing LAB. All G– bacteria potently up-regulated surface markers; however, these markers were not inhibited by weakly IL-12- and TNF-{alpha}-inducing LAB. These much divergent DC stimulation patterns among intestinal bacteria, which encompass both antagonistic and synergistic relationships, support the growing evidence that the composition of the gut flora affects immune regulation and that compositional imbalances may be involved in disease etiology.

* Corresponding author. Mailing address: BioCentrum-DTU, Biochemistry and Nutrition Group, Technical University of Denmark, Building 224, DK-2800 Kgs. Lyngby, Denmark. Phone: 45 45252752. Fax: 45 45886307. E-mail: lhz{at}biocentrum.dtu.dk.

{dagger} Present address: Novo Nordisk A/S, Bagsvoerd, Denmark.

Clinical and Vaccine Immunology, March 2006, p. 365-375, Vol. 13, No. 3
1071-412X/06/$08.00+0     doi:10.1128/CVI.13.3.365-375.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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  • Fink, L. N., Zeuthen, L. H., Christensen, H. R., Morandi, B., Frokiaer, H., Ferlazzo, G. (2007). Distinct gut-derived lactic acid bacteria elicit divergent dendritic cell-mediated NK cell responses. Int Immunol 19: 1319-1327 [Abstract] [Full Text]  


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