Información del artículo
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.
Keywords:
Tuberculosis
Immunology
Pathogenesis
Bacterial latency
Macrophages
Resumen
El enfrentamiento entre los patógenos invasivos y los sistemas defensivos del huésped implica interacciones celulares y moleculares. En el presente artículo se discuten los factores de virulencia como triunfos, favoreciendo el éxito de la contienda a favor del bacilo tuberculoso (Mycobacterium tuberculosis). Éste desarrolla un número de constituyentes moleculares que pueden interferir con la presentación antigénica y la función Toll receptor, deteriorando las defensas inmunes del huésped, así como respuestas al estrés que enlentecen su ciclo celular hasta convertirlo en no replicante. Aunque el recuento bajo de bacilos latentes previene su detección directa, postulamos que retienen cierta capacidad de sobrevivir dentro de macrófagos espumosos y en las partes necróticas de los granulomas pulmonares. Mientras que el circuito natural del fluido alveolar hacia las vías respiratorias superiores es el responsable de la eliminación de bacilos, su retorno para generar aerosoles de forma fisiológica también implica la posibilidad de que con él ciertos bacilos puedan reinfectar de forma endógena los pulmones y transmitir la infección a nuevos individuos. Consideramos, pues, la tuberculosis latente como un proceso continuo, en contraposición al concepto de la existencia de bacilos largamente durmientes y con capacidad de resucitar. Creemos, además, que la fibrosis del tejido conectivo de los pulmones, capaz en ocasiones de encapsular lesiones pulmonares, es la responsable de frenar el drenaje y la diseminación de bacilos, limitando el ciclo reinfectivo. En conclusión, la novedad de nuestra visión radica en la percepción dinámica de la latencia de M. tuberculosis y sus consecuencias sobre la patogénesis de la tuberculosis.
Palabras clave:
Tuberculosis
Inmunología
Patogénesis
Latencia bacteriana
Macrófagos
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