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

Mansour Mohamadzadeh*, Erika A. Pfeiler, Jeffrey B. Brown, Mojgan Zadeh, Matthew Gramarossa, Elizabeth Managlia, Praveen Bere, Bara Sarraj, Mohammad W. Khan, Krishna Chaitanya Pakanati, M. Javeed Ansari, Sarah O'Flaherty, Terrence Barrett, Todd R. Klaenhammer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

188 Scopus citations


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 LTAnegative 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 highT 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.

Original languageEnglish (US)
Pages (from-to)4623-4630
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America
Issue numberSUPPL. 1
StatePublished - Mar 15 2011


  • Antiinflammatory
  • Innate immunity
  • Lactobacilli
  • Toll-like receptor 2

ASJC Scopus subject areas

  • General


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