title: A Single ssDNA Aptamer Binding to Mannose-Capped Lipoarabinomannan of Bacillus Calmette-Guérin Enhances Immunoprotective Effect against Tuberculosis.
abstract: Because Mycobacterium bovis, termed bacillus Calmette-Guérin (BCG), the only available used tuberculosis (TB) vaccine, retains immunomodulatory properties that limit its protective immunogenicity, there are continuous efforts to identify the immunosuppression mechanism as well as new strategies for improving the immunogenicity of BCG. Here, an ssDNA aptamer "antibody" BM2 specifically bound to the mannose-capped lipoarabinomannan (ManLAM) of BCG was selected. BM2 significantly blocked ManLAM-mannose receptor (MR) binding, triggered ManLAM-CD44 signaling, and enhanced M1 macrophage and Th1 activation via cellular surface CD44 in vitro and in vivo. BM2 enhanced immunoprotective effects of BCG against virulent Mycobacterium tuberculosis H37Rv infection in mice and monkeys models. Thus, we report a new mechanism of the interaction between ManLAM and CD44 on macrophages and CD4(+) T cells and reveal that ManLAM-binding membrane molecule CD44 is a novel target for the enhancement of BCG immunogenicity, and BM2 has strong potential as an immune enhancer for BCG.
authors.affiliation: State Key Laboratory of Virology and Medical Research Institute, Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, Wuhan University School of Medicine , Wuhan 430071, P. R. China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Virology and Medical Research Institute, Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, Wuhan University School of Medicine , Wuhan 430071, P. R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Virology and Medical Research Institute, Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, Wuhan University School of Medicine , Wuhan 430071, P. R. China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Virology and Medical Research Institute, Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, Wuhan University School of Medicine , Wuhan 430071, P. R. China.|Department of Clinical Oncology, Huai'an First People's Hospital, Nanjing Medical University , Huai'an 223300, China.
authors.forename: Qilong
authors.initials: Q
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Virology and Medical Research Institute, Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, Wuhan University School of Medicine , Wuhan 430071, P. R. China.|Department of Clinical Laboratory, The Second Hospital of Wuhu , Wuhu 241000, Anhui Province, China.
authors.forename: Xiao-Lei
authors.initials: XL
authors.lastname: Tang
authors.affiliation: Shanghai Institute of Materia Medica , Shanghai 201203, China.
authors.forename: Kan
authors.initials: K
authors.lastname: Ding
authors.affiliation: College of Chemistry and Molecular Sciences, Wuhan University , Wuhan 430072, Hubei Province, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Virology and Medical Research Institute, Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, Wuhan University School of Medicine , Wuhan 430071, P. R. China.
authors.forename: Xiao-Lian
authors.initials: XL
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D017951:Antigen Presentation; D052157:Aptamers, Nucleotide / Q000378:metabolism*; D001500:BCG Vaccine / Q000276:immunology* / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000378:metabolism*; D018960:Hyaluronan Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism*; D008253:Macaca mulatta; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008358:Mannose / Q000378:metabolism*; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D052156:SELEX Aptamer Technique; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D052157:Aptamers, Nucleotide; D001500:BCG Vaccine; D004277:DNA, Single-Stranded; D018960:Hyaluronan Receptors; D008070:Lipopolysaccharides; C050016:lipoarabinomannan; D008358:Mannose