title: Pretreatment with Mycobacterium avium-derived lipids attenuates the             response of murine macrophages to components of Mycobacterium tuberculosis.
abstract: The high prevalence of Mycobacterium tuberculosis (MTB) despite widely available Bacille Calmette-Guerin (BCG) vaccination may be associated with Mycobacterium avium (M. avium), which may influence the host response to MTB. In this study, we demonstrate that pretreatment of murine macrophages with low-dose Mycobacterium avium-derived lipids (MALs), but not Escherichia coli-derived lipids (ELs), attenuates the clearance of intracellular Mycobacterium bovis BCG (M. bovis BCG) and the production of TNF-α, IL-6, IL-12 and nitric oxide (NO) following stimulation with purified protein derivatives (PPD) or heat-inactivated M. bovis BCG in vitro. Furthermore, a significant decrease in NF-κB activity was observed in MALs-pretreated RAW264.7 cells that were co-transfected with pSV-β-galactosidase and pGL4.32[luc2P/NF-κB-RE/Hygro] prior to stimulation with PPD or heat-inactivated M. bovis BCG. In contrast, IRAK-M, an inhibitor of NF-κB activation, was increased in these cells. This observed hyporesponsiveness is not related to the expression of Toll-like receptor 2 (TLR2). In conclusion, pretreatment with low-dose MALs can induce hyporesponsiveness to MTB components in murine macrophages.
authors.affiliation: Department of Immunology, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong 510515, PR China.
authors.forename: Daqing
authors.initials: D
authors.lastname: Yang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Yiguo
authors.initials: Y
authors.lastname: Chen
authors.forename: Delong
authors.initials: D
authors.lastname: Jiao
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Hou
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Fu
mesh_terms: D000818:Animals; D001681:Biological Assay; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004926:Escherichia coli / Q000737:chemistry; D005260:Female; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D042541:Intracellular Space / Q000187:drug effects / Q000382:microbiology; D008055:Lipids / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects* / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009162:Mycobacterium avium / Q000737:chemistry* / Q000187:drug effects; D009163:Mycobacterium bovis / Q000187:drug effects / Q000254:growth & development; D009169:Mycobacterium tuberculosis / Q000737:chemistry* / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D009573:Nitrites / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014373:Tuberculin / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; D008055:Lipids; D016328:NF-kappa B; D009573:Nitrites; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014373:Tuberculin; D009569:Nitric Oxide; D053592:Interleukin-1 Receptor-Associated Kinases; C507772:Irak3 protein, mouse