title: Induction of murine macrophage TNF-alpha synthesis by Mycobacterium avium is modulated through complement-dependent interaction via complement receptors 3 and 4 in relation to M. avium glycopeptidolipid.
abstract: We studied whether complement receptor (CR) mediated Mycobacterium avium interaction modulated macrophage TNF-alpha expression. Compared to control conditions, infections performed with C3-depletion yielded significantly higher TNF-alpha levels. Blockage of the CR4 iC3b site yielded increases in TNF-alpha for all morphotypic variants of a virulent serovar-8 strain (smooth transparent (SmT), smooth opaque (SmO), serovar-specific glycopeptidolipid (ssGPL) deficient knockout mutant) whereas CR3 blockage increased TNF-alpha only for SmT and ssGPL-deficient strains. Thus, complement-mediated binding of M. avium to CR3 and CR4 was shown to modulate TNF-alpha expression. The differential activation of morphotypic and isogenic variants of a single strain provides an excellent model system to delineate signaling pathways.
authors.affiliation: Division of Infectious Diseases, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
authors.forename: Vida R
authors.initials: VR
authors.lastname: Irani
authors.forename: Joel N
authors.initials: JN
authors.lastname: Maslow
mesh_terms: D000818:Animals; D002460:Cell Line; D003176:Complement C3 / Q000378:metabolism*; D003181:Complement C4 / Q000378:metabolism*; D006017:Glycolipids / Q000235:genetics / Q000378:metabolism; D006020:Glycopeptides / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D015269:Mycobacterium avium Complex / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015270:Mycobacterium avium-intracellulare Infection / Q000276:immunology / Q000382:microbiology; D011951:Receptors, Complement / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D003176:Complement C3; D003181:Complement C4; D006017:Glycolipids; D006020:Glycopeptides; D011951:Receptors, Complement; D014409:Tumor Necrosis Factor-alpha