Altered human gut dendritic cell properties in ulcerative colitis are reversed by Lactobacillus plantarum extracellular encrypted peptide STp

Abstract

Scope:The human/microbiota cross-talk is partially mediated by bacteria-derived peptides like Serine-Threonine peptide (STp), which is resistant to gut proteolysis, is found in the human healthy colon and induces regulatory properties on gut dendritic cells (DCs); here we characterized human gut DC in ulcerative colitis (UC) patients and studied the effect of STp on their properties. Methods and results: Human colonic DC from healthy controls and UC patients were isolated, conditioned for 24 h +/− STp and characterized by flow cytometry, immunohistochemistry, and electron microscopy. Expression of immature DC markers DC-SIGN and ILT3, and Tolllike receptors were increased on gut UC-DC. Langerin (involved in phagocytosis), lymph node homing marker CCR7, and activation markers CD40/CD80/CD86 were decreased in UC. Gut DC had restricted stimulatory capacity for T-cells in UC. Conditioning of DC with STp in vitro reduced Toll-like receptor expression, increased CD40 and CD80 expression, and restored their stimulatory capacity. Conclusion: Colonic DCs display an abnormal immature phenotype in UC, which was partially restored following STp treatment. Bacteria-derived metabolites, like STp, seem to have a role in gut homeostasis that is missing in UC so they might lead a new era of probiotic products setting the basis for nondrug dietary therapy in inflammatory bowel disease.

The Surface-Associated Exopolysaccharide of Bifidobacterium longum 35624 Plays an Essential Role in Dampening Host Proinflammatory Responses and Repressing Local T H 17 Responses

“…The bifidobacterial cell wall is a complex arrangement of macromolecules, consisting of a thick peptidoglycan layer that surrounds the cytoplasmic membrane, which is decorated with other glycopolymers, such as (lipo)teichoic acids, polysaccharides, and proteins, all of which may influence the immune response (45,46) A few examples include the cell wall-associated proteins p40 and p75 from L. casei subsp. rhamnosus GG, the S-layer protein from Lactobacillus acidophilus, and the STp peptide from Lactobacillus plantarum (47)(48)(49).…”

Extracellular molecular effectors mediating probiotic attributes

“…A few examples that belong to these types of molecular factors are the cell wall‐associated proteins p40 and p75 from Lactobacillus casei ssp. rhamnosus GG, the S‐layer protein from L. acidophilus , or the STp peptide encoded in the secreted protein D1 from L. plantarum (Konstantinov et al ., ; Seth et al ., ; Yan et al ., ; Bernardo et al ., ; Al‐Hassi et al ., ). In L. casei BL23, the presence of two proteins associated with the bacterial surface, and which can also be secreted, was reported (Bäuerl et al ., ).…”

MAHMI database: a comprehensive MetaHit-based resource for the study of the mechanism of action of the human microbiota

“…This is a very promising field and, for instance, recent results have revealed that a peptide encrypted in a Lactobacillus plantarum extracellular protein, more concisely an aggregation factor, is able to modulate the immune status of both intestinal and monocyte-differentiated DCs, including cytokine secretion and toll-like receptors (TLR) expression (40, 41). By querying the content of MAHMI database, the researcher will easily have insights about the potential bioactivity of the user-submitted amino acid sequence.…”