Regulation of induced colonic inflammation byLactobacillus acidophilusdeficient 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 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 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.antiinflammatory | lactobacilli | Toll-like receptor 2 | innate immunity

Bacteroides fragilis polysaccharide A is necessary and sufficient for acute activation of intestinal sensory neurons

“…However, bacterial components such as glycolipids may be important for signalling between some probiotics and host. For example, certain Lactobacillus species in which capsular lipoteichoic acid is absent or D-alanine depleted, switch from being pro-to anti-inflammatory 16,17 in vivo and in vitro, and, with respect to visceral pain in rats, to being antinociceptive 18 .…”

Lactobacillus acidophilus, un futur outil thérapeutique dans le traitement des maladies inflammatoires chroniques de l’intestin ?

“…Celles-ci activent alors des lymphocytes T régulateurs permettant un contrôle de l'inflammation intestinale dans un modèle de colite expérimen-tale chez la souris [11]. Les chercheurs avaient ainsi postulé que cette protéine glycosylée pourrait être reconnue par la lectine de type C DC-SIGN, exprimée par les cellules dendritiques, dont on sait qu'elle contrôle la régulation des réponses immunitaires [12].…”

“…Cependant, chez les patients obèses, la fréquence des lymphocytes iNKT dans le tissu adipeux omental diminue significativement [5]. Des expériences effectuées avec des modèles murins suggèrent que les lymphocytes iNKT ont une fonction régulatrice anti-inflammatoire dans le tissu adipeux [11]. La diminution des lymphocytes iNKT au cours de l'obé-sité contribuerait à la perte de l'homéos-tasie dans le tissu adipeux.…”

Advancing the use ofLactobacillus acidophilussurface layer protein A for the treatment of intestinal disorders in humans

“…[10][11][12] Analyzed mechanisms suggested that the induction of regulatory IL-10 C DCs and functional Tregs, activation of pErk1/2, and the downregulation of critical downstream signals (Akt1, p38) 13 are key elements involved in the amelioration of murine colitis in our models. [10][11][12][13][14] Furthermore, this L. acidophilus strain lacking LTA significantly diminished inflammation-promoting colonic polyposis in the Apc lox468 x TS4-Cre mouse model via the regulation of proinflammatory innate and T cell subsets.…”

“…[10][11][12] Analyzed mechanisms suggested that the induction of regulatory IL-10 C DCs and functional Tregs, activation of pErk1/2, and the downregulation of critical downstream signals (Akt1, p38) 13 are key elements involved in the amelioration of murine colitis in our models. [10][11][12][13][14] Furthermore, this L. acidophilus strain lacking LTA significantly diminished inflammation-promoting colonic polyposis in the Apc lox468 x TS4-Cre mouse model via the regulation of proinflammatory innate and T cell subsets. 9 Thus, we theorized that the cross-talk between a specific surface molecule expressed by the LTAdeficient L. acidophilus, called SlpA, with intestinal innate cells (e.g., DCs) not only suppresses pathogenic inflammation, but also potentially modulates the expression of epigenetically-regulated, colorectal cancer (CRC)-associated genes, 15 and restores gut homeostasis to ablate colonic polyps.…”