Regulation of induced colonic inflammation by Lactobacillus acidophilus deficient in lipoteichoic acid

• Published in: Proceedings of the National Academy of Sciences - PNAS 2011-03, Vol.108 (Supplement 1), p.4623-4630
• Main Authors: Mohamadzadeh, Mansour, Pfeiler, Erika A, Brown, Jeffrey B, Zadeh, Mojgan, Gramarossa, Matthew, Managlia, Elizabeth, Bere, Praveen, Sarraj, Bara, Khan, Mohammad W, Pakanati, Krishna Chaitanya, Ansari, M. Javeed, O'Flaherty, Sarah, Barrett, Terrence, Klaenhammer, Todd R
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Autoimmunity; Autoimmunity - immunology; Beta cells; Biological Sciences; biosynthesis; CD4 antigen; CD4-positive T-lymphocytes; CD4-Positive T-Lymphocytes - immunology; Cell activation; Cell surface; Clostridium; Colitis; Colitis - chemically induced; Colitis - immunology; Colitis - microbiology; Colloquium Papers; Cytokines; Data processing; Dendritic cells; dextran; Dextran sulfate; Dextran Sulfate - toxicity; DNA Primers - genetics; Flow Cytometry; Fluorescent Antibody Technique; Foxp3 protein; Gene Deletion; Gene expression regulation; Gene Expression Regulation - immunology; genes; Homeodomain Proteins - genetics; Homeostasis; humans; Immunoregulation; Inflammation; Inflammatory bowel diseases; Interleukin 10; Interleukin 12; Interleukin-10 - genetics; Intestine; Lactobacillus acidophilus; Lactobacillus acidophilus - metabolism; Lipopolysaccharides - deficiency; Lipoteichoic acid; lipoteichoic acids; Lymphocytes T; Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular modelling; Mucosa; Myeloid Differentiation Factor 88 - genetics; Pattern recognition; Polarization; Polymerase Chain Reaction; probiotics; receptors; Sodium; sodium sulfate; T lymphocytes; Teichoic Acids; Transferases (Other Substituted Phosphate Groups) - genetics; Tumor necrosis factor- alpha
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1005066107

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⁺CD45RBhighT 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.