Identification of Lactobacillus plantarum genes modulating the cytokine response of human peripheral blood mononuclear cells
1 TI Food & Nutrition, Nieuwe Kanaal 9A, 6709PA, Wageningen, The Netherlands
2 NIZO food research, P.O. Box 20, 6710 BA Ede, The Netherlands
3 Host-Microbe Interactomics, Animal Sciences, Wageningen University, P.O. Box 338, 6700 AH Wageningen, The Netherlands
4 Vrije Universiteit Amsterdam, Faculty of Earth and Life Sciences, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands
5 Kluyver Centre for Genomics of Industrial Fermentation, P.O. Box 5057, 2600 GA, Delft, The Netherlands
6 Immunoendocrinology, Pathology and Medical Biology, University Medical Centre Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands
7 Laboratory of Microbiology, Wageningen University, Dreijenplein 10, 6703 HB Wageningen, The Netherlands
8 Department of Food Science and Technology, One Shields Avenue, Davis, CA 95616, USA
BMC Microbiology 2010, 10:293 doi:10.1186/1471-2180-10-293Published: 16 November 2010
Modulation of the immune system is one of the most plausible mechanisms underlying the beneficial effects of probiotic bacteria on human health. Presently, the specific probiotic cell products responsible for immunomodulation are largely unknown. In this study, the genetic and phenotypic diversity of strains of the Lactobacillus plantarum species were investigated to identify genes of L. plantarum with the potential to influence the amounts of cytokines interleukin 10 (IL-10) and IL-12 and the ratio of IL-10/IL-12 produced by peripheral blood mononuclear cells (PBMCs).
A total of 42 Lactobacillus plantarum strains isolated from diverse environmental and human sources were evaluated for their capacity to stimulate cytokine production in PBMCs. The L. plantarum strains induced the secretion of the anti-inflammatory cytokine IL-10 over an average 14-fold range and secretion of the pro-inflammatory cytokine IL-12 over an average 16-fold range. Comparisons of the strain-specific cytokine responses of PBMCs to comparative genome hybridization profiles obtained with L. plantarum WCFS1 DNA microarrays (also termed gene-trait matching) resulted in the identification of 6 candidate genetic loci with immunomodulatory capacities. These loci included genes encoding an N-acetyl-glucosamine/galactosamine phosphotransferase system, the LamBDCA quorum sensing system, and components of the plantaricin (bacteriocin) biosynthesis and transport pathway. Deletion of these genes in L. plantarum WCFS1 resulted in growth phase-dependent changes in the PBMC IL-10 and IL-12 cytokine profiles compared with wild-type cells.
The altered PBMC cytokine profiles obtained with the L. plantarum WCFS1 mutants were in good agreement with the predictions made by gene-trait matching for the 42 L. plantarum strains. This study therefore resulted in the identification of genes present in certain strains of L. plantarum which might be responsible for the stimulation of anti- or pro-inflammatory immune responses in the gut.