title: Cell-autonomous effector mechanisms against mycobacterium tuberculosis.
abstract: Few pathogens run the gauntlet of sterilizing immunity like Mycobacterium tuberculosis (Mtb). This organism infects mononuclear phagocytes and is also ingested by neutrophils, both of which possess an arsenal of cell-intrinsic effector mechanisms capable of eliminating it. Here Mtb encounters acid, oxidants, nitrosylating agents, and redox congeners, often exuberantly delivered under low oxygen tension. Further pressure is applied by withholding divalent Fe²⁺, Mn²⁺, Cu²⁺, and Zn²⁺, as well as by metabolic privation in the form of carbon needed for anaplerosis and aromatic amino acids for growth. Finally, host E3 ligases ubiquinate, cationic peptides disrupt, and lysosomal enzymes digest Mtb as part of the autophagic response to this particular pathogen. It is a testament to the evolutionary fitness of Mtb that sterilization is rarely complete, although sufficient to ensure most people infected with this airborne bacterium remain disease-free.
authors: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut 06510.
authors: John D
authors: JD
authors: MacMicking
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides; D002244:Carbon / Q000378:metabolism; D002412:Cations / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007113:Immunity, Innate; D007501:Iron / Q000378:metabolism; D008247:Lysosomes; D008264:Macrophages / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D018384:Oxidative Stress / Q000276:immunology; D010586:Phagocytes / Q000276:immunology*; D017382:Reactive Oxygen Species; D018167:Receptors, Calcitriol / Q000276:immunology; D017471:Receptors, Interferon / Q000276:immunology; D017472:Receptors, Interleukin-1 / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: D000596:Amino Acids; D023181:Antimicrobial Cationic Peptides; D002412:Cations; D017382:Reactive Oxygen Species; D018167:Receptors, Calcitriol; D017471:Receptors, Interferon; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D051193:Toll-Like Receptors; D002244:Carbon; D007501:Iron