Infection of murine striated muscle with <i>Mycobacterium leprae</i>: A study by light and electron microscopy

Esiri, Margaret M.; Weddell, A. G. M.; Rees, R. J. W.

doi:10.1002/path.1711060203

Cited by 12 publications

(9 citation statements)

References 7 publications

(2 reference statements)

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“…The presence of emetine reduced the TNF requirement approximately 1,000-fold at all concentrations of sonicate. Results were similar with one culture filtrate (3 weeks) of H37Rv (data not shown), although such filtrates contain many intracellular components which leak from dead organisms (1) so that the significance of this observation is uncertain. However, these experiments show that uptake of bacilli is not essential for induction of increased sensitivity to TNF.…”

Section: -supporting

confidence: 60%

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Effect of mycobacteria on sensitivity to the cytotoxic effects of tumor necrosis factor

Filley

Rook

1991

Infect Immun

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Unlike Mycobacterium leprae, Mycobacterium tuberculosis is not found inside cells other than macrophages and polymorphonuclear cells in vivo, yet previous work has revealed that in vitro it readily enters all cell lines tested. Moreover, these cells are not killed by the intracellular mycobacteria. We report here that when fibroblasts take up live (but not killed) M. tuberculosis H37Rv, they develop greatly increased sensitivity to the toxic effects of tumor necrosis factor (TNF) whether the cell line is inherently sensitive to TNF or not. Ultrasonically disrupted M. tuberculosis also has this property. The increased sensitivity is seen in the absence of metabolic inhibitors, although addition of emetine, an inhibitor of protein synthesis, causes the effect to manifest itself earlier and at a lower concentration of TNF. In contrast, infection with Mycobacterium bovis bacillus Calmette-Guerin induces little or no increased sensitivity to TNF, whereas Mycobacterium avium and M. tuberculosis H37Ra have intermediate sensitivities. We discuss the possibility that virulent tuberculosis strains produce a factor which distorts the normal protective function of TNF, rendering it toxic to host tissues and leading to the classical immunopathology of tuberculous lesions.

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Section: -supporting

confidence: 60%

“…Mycobacterium leprae is found within a wide range of cell types in vivo, including muscle cells, endothelial cells, neurons, Schwann cells, and fibroblasts (2)(3)(4). In contrast, Mycobacterium tuberculosis is found in extracellular sites or within phagocytic cells but almost never inside nonphagocytic cells such as those which can harbor M. leprae.…”

mentioning

confidence: 99%

Effect of mycobacteria on sensitivity to the cytotoxic effects of tumor necrosis factor

Filley

Rook

1991

Infect Immun

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“…In con trast, M. tuberculosis rapidly kills macrophages which take it up, and the organisms are not seen inside non professional phagocytes in vivo. This is particularly odd since Mycobacterium leprae is regularly found inside a large range of non-professional cell types in vivo [16], While investigating this phenomenon we have observed that fibroblasts infected with M. tuberculosis become ex quisitely sensitive to the toxic effects of TNF, even in the absence of metabolic inhibitors such as actinomycin D or emetine which are usually added to TNF bioassays. Indeed, a cell line (a gift from Dr. N. Matthews, Cardiff, UK), which is inherently resistant to TNF, can be killed when infected with this organism [Filley et al, in prepa ration], Smaller, but still very significant increases in sensitivity to TNF are seen when cells are incubated in crude supernatants of M. tuberculosis, and it will be important to identify the component responsible.…”

Section: Production By M Tuberculosis Of a Factor Which 'Perverts' Tmentioning

confidence: 96%

New Insights into the Immunopathology of Tuberculosis

Rook¹,

Attiyah²,

Filley³

1991

Pathobiology

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Tuberculosis is characterised by fever, weight loss and necrosis in both lesions and tuberculin skin test sites (Koch phenomenon), although the antigens of Mycobacterium tuberculosis are not directly toxic to the tissues. The tissue damage appears to be due to several interacting factors. First, M. tuberculosis induces an immunoregulatory disorder of which a raised percentage of agalactosyl IgG is a marker. This is seen also in rheumatoid arthritis and Crohn’s disease and is associated with tissue-damaging inflammation. Subsequently, several properties of M. tuberculosis exacerbate this disorder by triggering cytokine release, and rendering tissues sensitive to the toxicity of tumor necrosis factor (TNF). Moreover, M. tuberculosis, but not bacillus Calmette-Guérin or several Mycobacterium avium strains, produces a factor which increases the toxicity of TNF for individual cells. Thus, M. tuberculosis may distort the normal protective role of TNF so that this cytokine becomes toxic to the host. The immunoregulatory disorder associated with agalactosyl IgG appears to be susceptible to immunotherapy, so novel types of treatment for the immunopathological component of tuberculosis are being explored.

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“…In experimental leprosy in the mouse, which is primarily a blood-borne infection, the main site of bacterial multiplication from a very early stage is muscle (Weddell, Palmer and Rees, 1971;Esiri, Weddell and Rees, 1972); though others have found the majority of organisms to be in macrophages during the log phase (Evans and Levy, 1972), or in fibroblasts (Shepard), and only later were they found in muscle. As regards human infections the present study brings out two points, that the optimum growth site depends to a considerable extent on the level of immunity, and that for a given level of immunity the site of maximum multiplication is not quite the same for an early lesion as it would be for a lesion in an established infection.…”

Section: Sites Of Bacterial Multiplication and Protectionmentioning

confidence: 99%

The pathogenesis of the early skin lesion in leprosy

Ridley

1973

The Journal of Pathology

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Infection of murine striated muscle with Mycobacterium leprae: A study by light and electron microscopy

Cited by 12 publications

References 7 publications

Effect of mycobacteria on sensitivity to the cytotoxic effects of tumor necrosis factor

Effect of mycobacteria on sensitivity to the cytotoxic effects of tumor necrosis factor

New Insights into the Immunopathology of Tuberculosis

The pathogenesis of the early skin lesion in leprosy

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