Mycobacterium bovis BCG increase the selected determinants of monocyte/macrophage activity, which were diminished in response to gastric pathogen Helicobacter pylori

Abstract

High antibiotic resistance of gastric pathogen Helicobacter pylori (Hp) and the ability to escape the host immune response prompt searching for therapeutic immunomodulators. Bacillus Calmette–Guerin (BCG) vaccine with Mycobacterium bovis (Mb) is a candidate for modulation the activity of immunocompetent cells, and onco-BCG formulation was successfully used in immunotherapy of bladder cancer. We determined the influence of onco-BCG on the phagocytic capacity of human THP-1 monocyte/macrophage cells, using the model of Escherichia coli bioparticles and Hp fluorescently labeled. Deposition of cell integrins CD11b, CD11d, CD18, membrane/soluble lipopolysaccharide (LPS) receptors, CD14 and sCD14, respectively, and the production of macrophage chemotactic protein (MCP)-1 were determined. Furthermore, a global DNA methylation, was also assessed. Human THP-1 monocytes/macrophages (TIB 202) primed or primed and restimulated with onco-BCG or Hp, were used for assessment of phagocytosis towards E. coli or Hp, surface (immunostaining) or soluble activity determinants, and global DNA methylation (ELISA). THP-1 monocytes/macrophages primed/restimulated with BCG showed increased phagocytosis capacity towards E. coli fluorescent particles, elevated expression of CD11b, CD11d, CD18, CD14, sCD14, increased MCP-1 secretion and DNA methylation. Preliminary results indicate that BCG mycobacteria may also induce the phagocytosis of H. pylori by THP-1 monocytes. Priming or priming and restimulation of monocytes/macrophages with BCG resulted in an increased activity of these cells, which was negatively modulated by Hp.

Spray-dried pH-sensitive chitosan microparticles loaded with Mycobacterium bovis BCG intended for supporting treatment of Helicobacter pylori infection

“…In this study, BMDM, as previously human THP-1 derived macrophages 29 , were treated for 24 h (induction-priming), with M. bovis BCG, and then the engulfment capacity of macrophages was evaluated. Furthermore, the influence of macrophage priming with mycobacteria on CD11b integrin expression and the level of total DNA methylation was determined.…”

“…CHI, CHI-Plur and CHI-GlcNAc solutions were prepared as described above. Then, 1 mL of M. bovis onco-BCG 3 × 10 8 CFU/mL was added to each type of solution, previously labelled with BacLight fluorescent dye tracer for 30 min at room temperature, which penetrates only into living cells, as previously described 29 . The labelled bacteria were then added to the prepared CHI solutions, and spray-dried as described above.…”

“…The guinea pig bone marrow macrophages were isolated to complete RPMI-1640 culture medium (cRPMI) from tibias and femurs as previously described 29 . Cells were adjusted to the density of 5 × 10 6 cells/mL in cRPMI and underwent stimulation with M. bovis BCG or live H. pylori reference strain CCUG17874 (Culture Collection, University of Gothenburg, Gothenburg, Sweden), which was cultured under microaerophilic conditions according to the previously described procedure 13 .…”

“…It was shown that priming and/or restimulation of human THP-1 monocytes or THP-1 derived macrophages with onco-BCG formulation resulted in increased phagocytic activity of these cells towards fluorescently labelled Escherichia coli ( E. coli ). It was accompanied by elevated deposition of cell surface receptors (CD11b, CD11d, CD18, CD14, sCD14) involved in phagocytosis, and with the production of macrophage chemotactic protein-1 (MCP-1) 29 .…”

Drug repurposing for cancer therapy

“…In addition, BCG was found to augment the phagocytic capacity of human THP-1 monocytes/macrophages against H. pylori, by increasing the expression of the surface integrins CD11b, CD11d and CD18, as well as the membrane and soluble lipopolysaccharide receptors CD14 and sCD14, ultimately reducing the incidence of GC. 263 Another study reported that intratumoral delivery of the prophylactic yellow fever vaccine (live 17D) into mice stimulated immune-mediated antitumor effects including the orchestration of cytotoxic T lymphocytes and suppression of Tregs. 264 Intriguingly, Tai et al found that administering a single dose of the influenza vaccine intramuscularly a day before surgery optimally activated NK cells in specific murine models.…”