title: The secret trumps, impelling the pathogenicity of tubercle bacilli.
abstract: Confrontation between invading microbial pathogens and host defense systems involves intricate cellular and molecular interactions. Here we discuss the virulence factors as trumps, overriding the contest in favor of the tubercle bacillus (Mycobacterium tuberculosis). It evolved a number of molecular constituents, which can interfere with antigen presentation and Toll receptor function, thus impairing immune defenses. It also evolved stress responses, which can drive its cell cycle into a non-replicating, low metabolic mode. Although the low counts of latent bacilli prevent their direct detection, we contend that they retain a capacity to survive for long periods in foamy macrophages and within the necrotic parts of lung granulomas. We attributed significance to drainage of M. tuberculosis by the alveolar fluid: while out-flow is responsible for the clearance, the reverse-flow has an important capacity to re-infect the lungs and to transmit the infection to new recipients. We consider the cycling between replicating and latent organisms to be a continuous process, which is a departure from the concept of long-lived dormant organisms, with a capacity to resuscitate. These aspects impinge also on the actions of isoniazid (INH) chemotherapy and on the topography of human lung lesions. Eventually, fibrosis of the connective tissue of the lungs is known to encapsulate lung lesions, thus limiting the impact of both outward and reverse drainage. In conclusion, the novelty of our views on M. tuberculosis-host interactions rests in the dynamic perception of M. tuberculosis latency and its evolutionary importance for the pathogenesis of tuberculosis.
authors.affiliation: Unitat de Tuberculosi Experimental, Departament de Microbiologia, Fundació Institut per a la Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Barcelona, Spain. pjcardona.igtp.germanstrias@gencat.cat
authors.forename: Pere-Joan
authors.initials: PJ
authors.lastname: Cardona
authors.forename: Juraj
authors.initials: J
authors.lastname: Ivanyi
mesh_terms: D000336:Aerosols; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D005355:Fibrosis; D054884:Host-Pathogen Interactions / Q000502:physiology*; D006801:Humans; D057131:Immune Evasion / Q000276:immunology; D007538:Isoniazid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D055985:Latent Tuberculosis / Q000453:epidemiology / Q000276:immunology / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology; D008954:Models, Biological; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D011650:Pulmonary Alveoli / Q000382:microbiology / Q000503:physiopathology; D014018:Tissue Distribution; D014375:Tuberculoma / Q000382:microbiology; D014376:Tuberculosis / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology* / Q000473:pathology / Q000635:transmission; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014774:Virulence / Q000502:physiology
chemical_list: D000336:Aerosols; D000942:Antigens, Bacterial; D000995:Antitubercular Agents; D001426:Bacterial Proteins; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D007538:Isoniazid