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

Authors :
Mojgan Zadeh
Terrence A. Barrett
Matthew Gramarossa
Jeffrey B. Brown
Mansour Mohamadzadeh
Elizabeth Managlia
Bara Sarraj
Praveen Bere
Sarah O'Flaherty
M. Javeed Ansari
Mohammad W. Khan
Krishna Chaitanya Pakanati
Erika A. Pfeiler
Todd R. Klaenhammer
Source :
Proceedings of the National Academy of Sciences. 108:4623-4630
Publication Year :
2011
Publisher :
Proceedings of the National Academy of Sciences, 2011.

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.

Details

ISSN :
10916490 and 00278424
Volume :
108
Database :
OpenAIRE
Journal :
Proceedings of the National Academy of Sciences
Accession number :
edsair.doi.dedup.....03abe522b096e7d9d1a59caf73313f6c
Full Text :
https://doi.org/10.1073/pnas.1005066107