title: Analysis of the immunomodulatory properties of two heat-killed mycobacterial preparations in a human whole blood model.
abstract: The significant role played by mycobacteria in modulating immune responses through enhancing the crosstalk between innate and adaptive immunity has been highlighted in several studies. Owing to their unique antigenic profile, heat killed (HK) preparations of rapid-growing mycobacteria, currently undergoing clinical development, have been assessed as adjuvant therapy in various diseases. The purpose of this study is to investigate the regulation of leukocyte surface receptors, in whole blood from healthy donors, following in vitro stimulation with HK Mycobacterium vaccae (M. vaccae) or M. obuense. We have demonstrated the ability of both mycobacterial preparations to target monocytes and neutrophils and to regulate the surface expression of selected adhesion receptors, antigen-presenting and costimulatory receptors, pattern recognition receptors, complement and Fc receptors, as well as cytokine/chemokine receptors. Toll-like receptors (TLRs) 1 and 2 were also shown to be involved in mediating the M. obuense-induced upregulation of selected surface receptors on monocytes. Whole blood stimulation with M. vaccae or M. obuense resulted in a significant increase in the secretion of a specific set of cytokines and chemokines. Both mycobacterial preparations induced strong antigen-specific proliferative responses in peripheral blood mononuclear cells. Collectively, our data shows that M. vaccae and M. obuense have the potential to act as potent immunomodulators. Future research based on these findings may reveal novel immune pathways induced by these preparations with potential implication for their use in diverse immunotherapeutic approaches.
authors.affiliation: School of Life Sciences, Faculty of Science, Engineering and Computing, Kingston University, Kingston upon Thames, Surrey KT1 2EE, United Kingdom; Faculty of Medicine and Medical Sciences, University of Balamand, 33 Amioun, Al Kurah, Lebanon. Electronic address: k1170034@kingston.ac.uk.
authors.forename: Samer
authors.initials: S
authors.lastname: Bazzi
authors.affiliation: School of Life Sciences, Faculty of Science, Engineering and Computing, Kingston University, Kingston upon Thames, Surrey KT1 2EE, United Kingdom. Electronic address: H.Modjtahedi@kingston.ac.uk.com.
authors.forename: Helmout
authors.initials: H
authors.lastname: Modjtahedi
authors.affiliation: Division of Clinical Sciences, St George's, University of London, London SW170RE, United Kingdom; Department of Academic Surgery, Royal Marsden Hospital, London SW3 6JJ, United Kingdom. Electronic address: mudans@aol.com.
authors.forename: Satvinder
authors.initials: S
authors.lastname: Mudan
authors.affiliation: The London Clinic, London W1G 6JA, United Kingdom. Electronic address: cakle@me.com.
authors.forename: Charles
authors.initials: C
authors.lastname: Akle
authors.affiliation: Faculty of Medicine and Medical Sciences, University of Balamand, 33 Amioun, Al Kurah, Lebanon. Electronic address: georges.bahr@balamand.edu.lb.
authors.forename: Georges M
authors.initials: GM
authors.lastname: Bahr
mesh_terms: D000276:Adjuvants, Immunologic; D015703:Antigens, CD / Q000378:metabolism; D039521:CD11c Antigen / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D056747:Immunomodulation; D016130:Immunophenotyping; D007962:Leukocytes / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009161:Mycobacterium / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D039521:CD11c Antigen; D018925:Chemokines; D016207:Cytokines; D006684:HLA-DR Antigens; D051193:Toll-Like Receptors
keywords: CD antigens; Human leukocytes; Immunomodulation; Mycobacteria