Characterization of genomic DNA of lactic acid bacteria for activation of plasmacytoid dendritic cells

• Published in: BMC microbiology Vol. 19; no. 1; p. 88
• Main Authors: Horie, Akira, Tomita, Yasuyuki, Ohshio, Konomi, Fujiwara, Daisuke, Fujii, Toshio
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 06.05.2019; BioMed Central; BMC
• Subjects: Animals; B cells; Bacteria; Bacterial genetics; Base Composition; Bioinformatics; Biological response modifiers; Cell activation; Cells, Cultured; Computational biology; Copy number; Correlation; CpG; CpG Islands; Dendritic cells; Dendritic Cells - immunology; Deoxyribonucleic acid; DNA; DNA, Bacterial - immunology; Female; Fragments; Gene loci; Genetic aspects; Genetic research; Genome, Bacterial; Genomes; Genomics; G + C contents; Interferon; Lactic acid; Lactic acid bacteria; Lactobacillales - genetics; Lactobacillus; Lactococcus lactis; Lactococcus lactis subsp. lactis LC-plasma; Leuconostoc mesenteroides; Mice; Mice, 129 Strain; MyD88 protein; Oligodeoxyribonucleotides; Pediococcus pentosaceus; Physiological aspects; Plasma; Plasmacytoid dendritic cells; Preferences; Probiotics; Screening; Strains (organisms); TLR9; TLR9 protein; Toll-like receptors; Type I interferon; TLR9; Lactococcus lactis subsp. lactis LC-plasma; Plasmacytoid dendritic cells; G + C contents; CpG; Type I interferon
• ISSN: 1471-2180; 1471-2180
• DOI: 10.1186/s12866-019-1458-y

Lactococcus lactis strain Plasma (LC-Plasma) possesses strong stimulatory activity for plasmacytoid dendritic cells (pDCs) via the TLR9-Myd88 pathway. To reveal the effective lactic acid bacteria (LAB) genome structure for pDCs stimulatory activity, we performed in vitro screening, using randomly selected 200 bp DNA fragments from the LC-Plasma genome. We found that the CpG motif copy number in the fragments was positively and significantly correlated with pDCs stimulatory activity (R = 0.491, p < 0.01). However, the determination coefficient (R ) was 0.24, which means other factors affecte activity. We found that the G + C contents of the fragment showed a significant negative correlation with activity (R = - 0.474, p < 0.01). The correlation between pDCs stimulatory activity and the copy number of CpG motifs was greatly increased when DNA fragments were stratified by G + C contents. We also performed bioinformatics analysis and a screening of LAB strains with high pDCs stimulatory activity. Species with a high copy number of CpG motifs in the low-G + C region of their genomes had higher probability of inducing high-pDCs stimulatory activity. L. lactis subsp. lactis, Leuconostoc mesenteroides, and Pediococcus pentosaceus were three typical examples of LAB that had high pDCs stimulatory activity. Our data suggested that the G + C content of DNA is one of the critical factors for pDCs stimulatory activity by DNA fragments. Furthermore, we found that the copy number in the low-G + C regions strongly affected the pDCs stimulatory activity of whole cells of LAB strains. These results should be useful for the design of new DNA fragments containing CpG motifs. This study also demonstrated an in silico screening method for identifying bacterial species that are able to activate pDCs.