Pathogenetic concepts of tuberculosis

Medlar, E. M.

doi:10.1016/0002-9343(50)90211-7

Cited by 30 publications

(20 citation statements)

References 1 publication

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“…This limited infection, known as Ghon’s complex, is comprised of a focal multiplication of the mycobacterium in the lung tissue associated with lymphangitis, infection and massive enlargement of the corresponding hilar draining lymph node. In approximately 95% of these individuals the inflammatory reaction is spontaneously contained and in many cases calcifies and persists for the remainder of the person’s life (28). However, several M. tuberculosis organisms remain viable for life, a condition known as latent or dormant tuberculosis (23, 28).…”

Section: Introductionmentioning

confidence: 99%

Guinea pig model of Mycobacterium tuberculosis latent/dormant infection

Kashino¹,

Napolitano²,

Skobe³

et al. 2008

Microbes and Infection

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Most experimental studies of latent or dormant tuberculosis infection have been conducted in murine models. Although guinea pigs are considered one of the animals that best reproduce human tuberculosis, surprisingly little data exist describing latent or dormant infection in these animals. The present work addresses this issue and shows that guinea pigs infected with a streptomycin auxotrophic mutant of Mycobacterium tuberculosis (strain 18b) replicate most of the known clinical, immunological, and pathological manifestations of this phase of the infectious process in humans. To establish infection, animals were inoculated with the mutant followed by administration of streptomycin for three weeks. Withdrawal of streptomycin caused microbial dormancy and few microorganisms remained viable and could be recovered from the animals' lungs and spleen several months later. Guinea pigs with dormant infection steadily gained weight and presented no clinical signs (scuff fur and lethargy) of active disease. The histopathology of the tuberculous lesions mimicked human lesions well. In addition, PBMC from infected animals strongly responded to stimulation with PPD or soluble culture filtrate proteins of M. tuberculosis throughout the duration of the experiment (six months). Finally, the tuberculin skin test (a clinical hallmark of latent infection) performed in guinea pigs infected with the auxotrophic mutant remarkably reproduced the response of humans to this test. Together, these findings confirm that infection of guinea pigs with M. tuberculosis strain 18b results in an infectious process that can be used as an interesting alternative model of latent or dormant tuberculosis infection in this animal specie.

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Section: Introductionmentioning

confidence: 99%

Guinea pig model of Mycobacterium tuberculosis latent/dormant infection

Kashino¹,

Napolitano²,

Skobe³

et al. 2008

Microbes and Infection

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“…This usually limited infection comprises a focal multiplication of the Mycobacterium in the lung tissue in association with lymphangitis, infection, and massive enlargement of the corresponding hilar draining lymph node. In approximately 95% of these individuals, the inflammatory reaction is spontaneously contained and in many cases calcifies and persists for the remainder of the person's life (26). Notwithstanding the clinical resolution of Ghon's complex, several M. tuberculosis organisms remain viable for life, a condition known as latent or dormant tuberculosis (21,26).…”

mentioning

confidence: 99%

“…In approximately 95% of these individuals, the inflammatory reaction is spontaneously contained and in many cases calcifies and persists for the remainder of the person's life (26). Notwithstanding the clinical resolution of Ghon's complex, several M. tuberculosis organisms remain viable for life, a condition known as latent or dormant tuberculosis (21,26). Primary tuberculosis usually stimulates strong and long-lasting cellular immune response to M. tuberculosis antigens, which can be detected even years later by the delayed-type hypersensitivity skin test (the purified protein derivative [PPD] or Mantoux test).…”

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confidence: 99%

Unique Model of Dormant Infection for Tuberculosis Vaccine Development

Kashino

Ovendale

Izzo

et al. 2006

Clin Vaccine Immunol

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Most individuals exposed to Mycobacterium tuberculosis become infected but hinder the infectious process in dormant foci, known as latent tuberculosis. This limited infection usually stimulates strong T-cell responses, which provide lifelong resistance to tuberculosis. However, latent tuberculosis is still poorly understood, particularly because of the lack of a reliable animal model of dormant infection. Here we show that inoculation of mice with a unique streptomycin-auxotrophic mutant of Mycobacterium tuberculosis recapitulates dormant infection. The mutant grows unimpaired in the presence of streptomycin and no longer grows but remains viable for long periods of time after substrate removal, shifting from the log growth phase to the latent stage, as indicated by augmented production of ␣-crystallin. Mice challenged with the mutant and inoculated with streptomycin for ϳ3 weeks developed a limited infection characterized by a low bacteriological burden and the presence of typical granulomas. After substrate withdrawal, the infection was hindered but few microorganisms remained viable (dormant) in the animals' tissues for at least 6 months. In addition, the animals developed both potent T-cell responses to M. tuberculosis antigens, such as early culture filtrate, Ag85B, and ESAT-6, and resistance to reinfection with virulent M. tuberculosis. Therefore, infection of mice or other animals (e.g., guinea pigs) with M. tuberculosis strain 18b constitutes a simple and attractive animal model for evaluation of antituberculosis vaccines in the context of an M. tuberculosis-presensitized host, a prevailing condition among humans in need of a vaccine.

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“…Most of the times this inflammatory reaction heals spontaneously and often calcifies and persists for the remainder of the person's life, a condition known as latent tuberculosis infection. 2,3 However, reactivation of latent tuberculosis leading to chronic pulmonary tuberculosis or adult tuberculosis may occur afterwards, even decades later because of intervening events such as malnutrition or immunosupression. 4 -6 Curiously, lung lesions during adult tuberculosis are most frequently localized in upper lung zones.…”

mentioning

confidence: 99%

Initiation of Acquired Immunity in the Lungs of Mice Lacking Lymph Nodes after Infection with Aerosolized Mycobacterium tuberculosis

Kashino¹,

Vallerskog

Martens

et al. 2010

The American Journal of Pathology

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Recent evidence points to lung draining lymph nodes as the site that initiates the immune response in mice infected with aerosolized Mycobacterium tuberculosis. Here we expanded these studies and showed that infection of mice that lack lymph nodes with aerosolized M. tuberculosis results in a massive mononuclear cell infiltrate in the lungs within 14 days postinfection. This infiltration clearly resembles an expansion of the bronchus-associated lymphoid tissue. As expected , no bronchus-associated lymphoid tissue was observed in M. tuberculosis-infected wild-type control mice. Importantly , acquired specific immune response to M. tuberculosis antigens could be detected in lung lymphocytes harvested from mice lacking lymph nodes as early as 14 days postinfection. In addition , the bacterial burden in these mice was indistinguishable from that observed in wild-type C57BL/6 control mice. These results indicate that in the absence of lymph nodes , priming of the immune response occurs in the lung tissues after infection of mice with aerosolized M. tuberculosis and clearly illustrate the enormous plasticity of the immune system to develop resistance to foreign pathogens. (Am J

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Pathogenetic concepts of tuberculosis

Cited by 30 publications

References 1 publication

Guinea pig model of Mycobacterium tuberculosis latent/dormant infection

Guinea pig model of Mycobacterium tuberculosis latent/dormant infection

Unique Model of Dormant Infection for Tuberculosis Vaccine Development

Initiation of Acquired Immunity in the Lungs of Mice Lacking Lymph Nodes after Infection with Aerosolized Mycobacterium tuberculosis

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