Bacterial Ghosts of Escherichia coli Drive Efficient Maturation of Bovine Monocyte-Derived Dendritic Cells

• Published in: PloS one Vol. 10; no. 12; p. e0144397
• Main Authors: Hajam, Irshad Ahmed, Dar, Pervaiz Ahmad, Appavoo, Elamurugan, Kishore, Subodh, Bhanuprakash, Veerakyathappa, Ganesh, Kondabattula
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15.12.2015; Public Library of Science (PLoS)
• Subjects: Analysis; Animals; Antigen Presentation - drug effects; Antigen-presenting cells; Antigens; Bacteria; Bacterial vaccines; Cattle; CD80 antigen; CD86 antigen; Cell Differentiation - drug effects; Cell envelopes; Cell proliferation; Cytokines; Cytokines - metabolism; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - drug effects; Deoxyribonucleic acid; DNA; E coli; Escherichia coli; Escherichia coli - drug effects; Escherichia coli - growth & development; Escherichia coli - metabolism; Escherichia coli - ultrastructure; Gene expression; Genetic aspects; Ghosts; Gram-negative bacteria; Granulocyte-macrophage colony-stimulating factor; Immune system; Inflammation; Interleukin 10; Interleukin 12; Interleukin 4; Kinetics; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Lymphocyte Culture Test, Mixed; Lymphocytes T; Major histocompatibility complex; Maturation; Mixed leukocyte reaction; Monocytes; Monocytes - cytology; Phenotype; Physiological aspects; Plasmids - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Stimulation; T cell receptors; Transcription, Genetic - drug effects; Tumor necrosis factor-α; Vaccines; India
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0144397

Bacterial ghosts (BGs) are empty cell envelopes derived from Gram-negative bacteria. They not only represent a potential platform for development of novel vaccines but also provide a tool for efficient adjuvant and antigen delivery system. In the present study, we investigated the interaction between BGs of Escherichia coli (E. coli) and bovine monocyte-derived dendritic cells (MoDCs). MoDCs are highly potent antigen-presenting cells and have the potential to act as a powerful tool for manipulating the immune system. We generated bovine MoDCs in vitro from blood monocytes using E. coli expressed bovine GM-CSF and IL-4 cytokines. These MoDCs displayed typical morphology and functions similar to DCs. We further investigated the E. coli BGs to induce maturation of bovine MoDCs in comparison to E. coli lipopolysaccharide (LPS). We observed the maturation marker molecules such as MHC-II, CD80 and CD86 were induced early and at higher levels in BG stimulated MoDCs as compared to the LPS stimulated MoDCs. BG mediated stimulation induced significantly higher levels of cytokine expression in bovine MoDCs than LPS. Both pro-inflammatory (IL-12 and TNF-α) and anti-inflammatory (IL-10) cytokines were induced in MoDCs after BGs stimulation. We further analysed the effects of BGs on the bovine MoDCs in an allogenic mixed lymphocyte reaction (MLR). We found the BG-treated bovine MoDCs had significantly (p<0.05) higher capacity to stimulate allogenic T cell proliferation in MLR as compared to the LPS. Taken together, these findings demonstrate the E. coli BGs induce a strong activation and maturation of bovine MoDCs.