title: Regulatory role of suppressive motifs from commensal DNA.
abstract: The microbiota contributes to the induction of both effector and regulatory responses in the gastrointestinal (GI) tract. However, the mechanisms controlling these distinct properties remain poorly understood. We previously showed that commensal DNA promotes intestinal immunity. Here, we find that the capacity of bacterial DNA to stimulate immune responses is species specific and correlated with the frequency of motifs known to exert immunosuppressive function. In particular, we show that the DNA of Lactobacillus species, including various probiotics, is enriched in suppressive motifs able to inhibit lamina propria dendritic cell activation. In addition, immunosuppressive oligonucleotides sustain T(reg) cell conversion during inflammation and limit pathogen-induced immunopathology and colitis. Altogether, our findings identify DNA-suppressive motifs as a molecular ligand expressed by commensals and support the idea that a balance between stimulatory and regulatory DNA motifs contributes to the induction of controlled immune responses in the GI tract and gut immune homeostasis. Further, our findings suggest that the endogenous regulatory capacity of DNA motifs enriched in some commensal bacteria could be exploited for therapeutic purposes.
authors.affiliation: Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: N
authors.initials: N
authors.lastname: Bouladoux
authors.forename: J A
authors.initials: JA
authors.lastname: Hall
authors.forename: J R
authors.initials: JR
authors.lastname: Grainger
authors.forename: L M
authors.initials: LM
authors.lastname: dos Santos
authors.forename: M G
authors.initials: MG
authors.lastname: Kann
authors.forename: V
authors.initials: V
authors.lastname: Nagarajan
authors.forename: D
authors.initials: D
authors.lastname: Verthelyi
authors.forename: Y
authors.initials: Y
authors.lastname: Belkaid
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000382:microbiology; D018899:CpG Islands / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004269:DNA, Bacterial / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D009670:Encephalitozoon cuniculi / Q000187:drug effects / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology; D018928:Immunity, Mucosal / Q000187:drug effects*; D007155:Immunologic Factors / Q000737:chemistry / Q000235:genetics; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D007778:Lactobacillus / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D059372:Nucleotide Motifs; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D019936:Probiotics / Q000494:pharmacology; D012967:Sodium Dodecyl Sulfate; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D014122:Toxoplasma / Q000187:drug effects / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D004269:DNA, Bacterial; D007155:Immunologic Factors; D009838:Oligodeoxyribonucleotides; D012967:Sodium Dodecyl Sulfate