title: Liposomal delivery of lipoarabinomannan triggers Mycobacterium tuberculosis specific T-cells.
abstract: Lipoarabinomannan (LAM) is a major cell wall component of Mycobacterium tuberculosis (Mtb). LAM specific human T-lymphocytes release interferon-γ (IFNγ) and have antimicrobial activity against intracellular Mtb suggesting that they contribute to protection. Therefore the induction of LAM-specific memory T-cells is an attractive approach for the design of a new vaccine against tuberculosis. A prerequisite for the activation of LAM-specific T-cells is the efficient uptake and transport of the glycolipid antigen to the CD1 antigen presenting machinery. Based on the hydrophobicity of LAM we hypothesized that packaging of LAM into liposomes will support the activation of T-lymphocytes. We prepared liposomes containing phosphatidylcholine, cholesterol, stearylated octaarginine and LAM via thin layer hydration method (LIPLAM). Flow cytometry analysis using fluorescently labelled LIPLAM showed an efficient uptake by antigen presenting cells. LAM delivered via liposomes was biologically active as demonstrated by the down-regulation of peroxisome proliferator activated receptor gamma (PPARγ) protein expression. Importantly, LIPLAM induced higher IFNγ production by primary human T-lymphocytes than purified LAM (2-16 times) or empty liposomes. These results suggest that the delivery of mycobacterial glycolipids via liposomes is a promising approach to promote the induction of M. tuberculosis specific T-cell responses.
authors.affiliation: Institute for Medical Microbiology and Hygiene, University Hospital Ulm, Albert Einstein Allee 11, 89081 Ulm, Germany. Electronic address: stephanie.kallert@uni-ulm.de.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kallert
authors.affiliation: Institute for Medical Microbiology and Hygiene, University Hospital Ulm, Albert Einstein Allee 11, 89081 Ulm, Germany. Electronic address: sebastian.zenk@uniklinik-ulm.de.
authors.forename: Sebastian F
authors.initials: SF
authors.lastname: Zenk
authors.affiliation: Central Unit Electron Microscopy, Albert-Einstein-Allee 11, 89081 Ulm, Germany. Electronic address: paul.walther@uni-ulm.de.
authors.forename: Paul
authors.initials: P
authors.lastname: Walther
authors.affiliation: Institute for Medical Microbiology and Hygiene, University Hospital Ulm, Albert Einstein Allee 11, 89081 Ulm, Germany. Electronic address: mark.grieshober@uniklinik-ulm.de.
authors.forename: Mark
authors.initials: M
authors.lastname: Grieshober
authors.affiliation: Institute for Organic Chemistry III/Macromolecular Chemistry, Albert-Einstein-Allee 11, 89081 Ulm, Germany. Electronic address: tanja.weil@uni-ulm.de.
authors.forename: Tanja
authors.initials: T
authors.lastname: Weil
authors.affiliation: Institute for Medical Microbiology and Hygiene, University Hospital Ulm, Albert Einstein Allee 11, 89081 Ulm, Germany. Electronic address: steffen.stenger@uniklinik-ulm.de.
authors.forename: Steffen
authors.initials: S
authors.lastname: Stenger
mesh_terms: D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D002784:Cholesterol / Q000737:chemistry; D018920:Coculture Techniques; D054884:Host-Pathogen Interactions; D057927:Hydrophobic and Hydrophilic Interactions; D007156:Immunologic Memory / Q000187:drug effects; D007371:Interferon-gamma / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D008081:Liposomes; D008213:Lymphocyte Activation / Q000187:drug effects*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009842:Oligopeptides / Q000737:chemistry; D047495:PPAR gamma / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry; D013228:Stearates / Q000737:chemistry; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D032581:Tuberculosis Vaccines / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology / Q000378:metabolism
chemical_list: C573415:IFNG protein, human; D008070:Lipopolysaccharides; D008081:Liposomes; D009842:Oligopeptides; D047495:PPAR gamma; D010713:Phosphatidylcholines; D013228:Stearates; D032581:Tuberculosis Vaccines; C050016:lipoarabinomannan; C487882:stearyl-octaarginine; D007371:Interferon-gamma; D002784:Cholesterol
keywords: Liposomes; Mycobacterium tuberculosis; T-lymphocytes; Vaccine