title: Regulation of induced colonic inflammation by Lactobacillus acidophilus deficient in lipoteichoic acid.
abstract: Imbalance in the regulatory immune mechanisms that control intestinal cellular and bacterial homeostasis may lead to induction of the detrimental inflammatory signals characterized in humans as inflammatory bowel disease. Induction of proinflammatory cytokines (i.e., IL-12) induced by dendritic cells (DCs) expressing pattern recognition receptors may skew naive T cells to T helper 1 polarization, which is strongly implicated in mucosal autoimmunity. Recent studies show the ability of probiotic microbes to treat and prevent numerous intestinal disorders, including Clostridium difficile-induced colitis. To study the molecular mechanisms involved in the induction and repression of intestinal inflammation, the phosphoglycerol transferase gene that plays a key role in lipoteichoic acid (LTA) biosynthesis in Lactobacillus acidophilus NCFM (NCK56) was deleted. The data show that the L. acidophilus LTA-negative in LTA (NCK2025) not only down-regulated IL-12 and TNFα but also significantly enhanced IL-10 in DCs and controlled the regulation of costimulatory DC functions, resulting in their inability to induce CD4(+) T-cell activation. Moreover, treatment of mice with NCK2025 compared with NCK56 significantly mitigated dextran sulfate sodium and CD4(+)CD45RB(high)T cell-induced colitis and effectively ameliorated dextran sulfate sodium-established colitis through a mechanism that involves IL-10 and CD4(+)FoxP3(+) T regulatory cells to dampen exaggerated mucosal inflammation. Directed alteration of cell surface components of L. acidophilus NCFM establishes a potential strategy for the treatment of inflammatory intestinal disorders.
authors.affiliation: Northwestern University, The Feinberg School of Medicine, Chicago, IL 60611, USA. m.zadeh@northwestern.edu
authors.forename: Mansour
authors.initials: M
authors.lastname: Mohamadzadeh
authors.forename: Erika A
authors.initials: EA
authors.lastname: Pfeiler
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Brown
authors.forename: Mojgan
authors.initials: M
authors.lastname: Zadeh
authors.forename: Matthew
authors.initials: M
authors.lastname: Gramarossa
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Managlia
authors.forename: Praveen
authors.initials: P
authors.lastname: Bere
authors.forename: Bara
authors.initials: B
authors.lastname: Sarraj
authors.forename: Mohammad W
authors.initials: MW
authors.lastname: Khan
authors.forename: Krishna Chaitanya
authors.initials: KC
authors.lastname: Pakanati
authors.forename: M Javeed
authors.initials: MJ
authors.lastname: Ansari
authors.forename: Sarah
authors.initials: S
authors.lastname: O'Flaherty
authors.forename: Terrence
authors.initials: T
authors.lastname: Barrett
authors.forename: Todd R
authors.initials: TR
authors.lastname: Klaenhammer
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000382:microbiology*; D017931:DNA Primers / Q000235:genetics; D016264:Dextran Sulfate / Q000633:toxicity; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000276:immunology*; D018398:Homeodomain Proteins / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D007779:Lactobacillus acidophilus / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000172:deficiency*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D016133:Polymerase Chain Reaction; D013682:Teichoic Acids; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics
chemical_list: D017931:DNA Primers; D018398:Homeodomain Proteins; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D013682:Teichoic Acids; C064658:RAG-1 protein; D016753:Interleukin-10; C009900:lipoteichoic acid; D016264:Dextran Sulfate; D017855:Transferases (Other Substituted Phosphate Groups); C037247:phosphatidylglycerol - membrane-oligosaccharide glycerophosphotransferase