New Conjugates of Tuftsin and Muramyl Dipeptide as Stimulators of Human Monocyte-Derived Dendritic Cells

Abstract

Muramyl dipeptide (MDP) and tuftsin are known biologically active compound displaying a significant influence on various cell populations of innate immune response. MDP, as a fragment of bacterial cell wall, stimulates not only macrophages and monocytes, but also dendritic cells. In contrast, little is known about tuftsin influence on these cells. Therefore it seemed vital to access whether tuftsin or its derivatives conjugated with MDP could influence the activity of this subpopulation of antigen presenting cells (APC). Immature dendritic cells (iDCs) were derived from human monocytes through eight-day tissue culture supplemented with hrIL-4 and hrGM-CSF. On the day 9 DCs were stimulated with newly synthesized conjugates of tuftsin and muramyl dipeptide. The influence of the examined compounds on the activity and maturity of monocyte-derived DCs was estimated by flow cytometry analysis. The flow cytometry analysis revealed that tuftsin and some of its analogues do stimulate maturation and activity of DCs but to a lesser extend in comparison to MDP. The obtained results suggest further development of the experiments concerning the influence of MDP and tuftsin analogues on the activity of dendritic cells.

Current Progress and Challenges in the Study of Adjuvants for Oral Vaccines

“…Muramyl dipeptide (MDP) is part of the bacterial cell wall and is delivered as a dipeptide with tuftsin, a biologically active compound [ 54 , 55 ]. Although their roles in oral immune adjustment have not been fully elucidated, it has been demonstrated that MDP and tuftsin can activate APCs [ 55 ].…”

“…Muramyl dipeptide (MDP) is part of the bacterial cell wall and is delivered as a dipeptide with tuftsin, a biologically active compound [ 54 , 55 ]. Although their roles in oral immune adjustment have not been fully elucidated, it has been demonstrated that MDP and tuftsin can activate APCs [ 55 ]. In the study by Jiang et al [ 54 ], the fusion protein of MDP and tuftsin was utilized as an adjuvant to modify the Lactobacillus casei vaccine strain.…”

Adjuvant Strategies for Lactic Acid Bacterial Mucosal Vaccines

“…As mentioned above, LAB activate NOD2 and this is mediated through MDP breakdown products of the bacterial peptidoglycan. The exact mechanism of immune enhancement by MDP in combination with tuftsin is not fully elucidated but has been shown to activate APCs [112].…”

Muramyl dipeptide-based analogs as potential anticancer compounds: Strategies to improve selectivity, biocompatibility, and efficiency

“…It has been found that one of the most interesting and medically relevant biological activities of MDP is the induction of pro-inflammatory release cytokines from human monocytes, which occurs via toll-like receptor (TLR) and NOD2-dependent signaling pathways ( 4 ). The oligomerization domains that bind the nucleotides NOD1 and NOD2 are involved in the recognition of PGN in the cytosol of cells ( 5 ). They are intracellularly related sensors of PGN and belong to the NOD-like receptor family of innate immunity proteins.…”

“…The innate immune system is activated when biological motifs that resemble pathogenic molecular patterns appear and are detected ( 5 ). The NOD1 receptor is activated by γ-D-glutamyl-meso-diaminopimelic acid, which is mainly found in gram-negative bacteria, and, in turn, the NOD2 pathogen recognition receptor molecule is a PGN sensor that recognizes the MDP generally present in all bacterial PGNs.…”