title: A single-stranded DNA aptamer against mannose-capped lipoarabinomannan enhances anti-tuberculosis activity of macrophages through downregulation of lipid-sensing nuclear receptor peroxisome proliferator-activated receptor γ expression.
abstract: Mannose-capped lipoarabinomannan (ManLAM) is an immunomodulatory epitope of Mycobacterium tuberculosis (Mtb). An aptamer (ZXL1) that specifically binds to ManLAM from the virulent Mtb H37Rv strain was previously generated and it was found that ZXL1 functions as an antagonist, inhibiting the ManLAM-induced immunosuppression of DCs. In the present study, it was found that ZXL1 inhibits Mtb entry into murine macrophages and that ZXL1 enhances IL-1β and IL-12 mRNA expression and cytokine production in ManLAM-treated macrophages but decreases IL-10 production. Inducible nitric oxide synthase expression in macrophages was upregulated in the presence of ZXL1 after stimulation with ManLAM. ZXL1 was also found to inhibit expression of lipid-sensing nuclear receptor peroxisome proliferator-activated receptor γ (PPAR-γ). These results suggest that ZXL1 promotes anti-tuberculosis activity through downregulation of PPAR-γ expression, which may contribute to M1 macrophage polarization and Mtb killing by macrophages.
authors.affiliation: State Key Laboratory of Virology and Medical Research Institue, Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, P. R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Virology and Medical Research Institue, Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, P. R. China.
authors.forename: Jiamin
authors.initials: J
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Virology and Medical Research Institue, Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, P. R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Virology and Medical Research Institue, Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, P. R. China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Virology and Medical Research Institue, Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, P. R. China.
authors.forename: Xiao-Lian
authors.initials: XL
authors.lastname: Zhang
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000378:metabolism*; D002478:Cells, Cultured; D004277:DNA, Single-Stranded / Q000378:metabolism; D015536:Down-Regulation; D004705:Endocytosis / Q000187:drug effects; D007155:Immunologic Factors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology*; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D047495:PPAR gamma / Q000096:biosynthesis*; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis
chemical_list: D052157:Aptamers, Nucleotide; D004277:DNA, Single-Stranded; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D047495:PPAR gamma; D018160:Receptors, Cytoplasmic and Nuclear; C050016:lipoarabinomannan
keywords: aptamer; inducible nitric oxide synthase; mannose-capped lipoarabinomannan