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.