Increased Expression of Fas Ligand in Human Tuberculosis and Leprosy Lesions: a Potential Novel Mechanism of Immune Evasion in Mycobacterial Infection

Mustafa, Tehmina; Bjune, T G; Jönsson, Roland; Hernández-Pando, Rogelio; Nilsen, Rune

doi:10.1046/j.1365-3083.2001.01020.x

Cited by 62 publications

(83 citation statements)

References 45 publications

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“…The Fas-FasL apoptosis of infected macrophages induced by CD8 ϩ T cells also appears to be important early in infection, in contrast to published in vitro studies (26,70) that examined the effects of this pathway on killing intracellular mycobacteria.…”

Section: T Cell Contributions To Immunitymentioning

confidence: 74%

Contribution of CD8+ T Cells to Control of Mycobacterium tuberculosis Infection

Sud

Bigbee

Flynn

et al. 2006

The Journal of Immunology

134

109

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Tuberculosis is the number one cause of death due to infectious disease in the world today. Understanding the dynamics of the immune response is crucial to elaborating differences between individuals who contain infection vs those who suffer active disease. Key cells in an adaptive immune response to intracellular pathogens include CD8+ T cells. Once stimulated, these cells provide a number of different effector functions, each aimed at clearing or containing the pathogen. To explore the role of CD8+ T cells in an integrative way, we synthesize both published and unpublished data to build and test a mathematical model of the immune response to Mycobacterium tuberculosis in the lung. The model is then used to perform a series of simulations mimicking experimental situations. Selective deletion of CD8+ T cell subsets suggests a differential contribution for CD8+ T cell effectors that are cytotoxic as compared with those that produce IFN-γ. We also determined the minimum levels of effector memory cells of each T cell subset (CD4+ and CD8+) in providing effective protection following vaccination.

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Section: T Cell Contributions To Immunitymentioning

confidence: 74%

Contribution of CD8+ T Cells to Control of Mycobacterium tuberculosis Infection

Sud

Bigbee

Flynn

et al. 2006

The Journal of Immunology

134

109

View full text Add to dashboard Cite

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“…These antigen-loaded cells expressed high levels of IL-10 and TNF-a. These heavily infected Mf also expressed large quantities of Fas ligand [54]. These Mf therefore might eliminate Fas-expressing cytotoxic lymphocytes, protecting themselves from being killed and thereby creating an intracellular sanctuary for M. tuberculosis [54].…”

Section: Resultsmentioning

confidence: 99%

“…These heavily infected Mf also expressed large quantities of Fas ligand [54]. These Mf therefore might eliminate Fas-expressing cytotoxic lymphocytes, protecting themselves from being killed and thereby creating an intracellular sanctuary for M. tuberculosis [54]. IL-10 is shown to have an antiapoptotic function, causing an increase in the survival of the cell [53,55,56].…”

Section: Resultsmentioning

confidence: 99%

In Situ Expression of Cytokines and Cellular Phenotypes in the Lungs of Mice with Slowly Progressive Primary Tuberculosis

Mustafa

Phyu²,

Nilsen³

et al. 2000

Scand J Immunol

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51:548±556The cellular phenotypes and the expression of cytokines were studied in the lungs of mice, using immunohistochemistry, during different phases of slowly progressive primary murine tuberculosis infection. During the ®rst phase the small focal lesions in healthy mice contained predominantly interleukin-2 (IL-2)-expressing cells. A small number of tumour necrosis factor-a (TNF-a)-, monocyte chemoattractant protein-1 (MCP-1)-and IL-10-expressing cells were also present. IL-4-expressing cells were not detected. During the second phase the mice became unwell, but the bacterial counts and the size of focal lesions stabilized. IL-4-expressing cells appeared. The IL-10-, TNF-a-and MCP-1-expressing cells increased in number. On progression to phase three, the mice became seriously unwell and died rapidly. The in¯ammation spread to < 80% of the lung parenchyma. There was a marked increase in the number of IL-10-expressing cells. Expression of other cytokines was similar to that observed in the second phase. In the lesions, 3±6% of the macrophages (Mf) containing mycobacterial antigens expressed high levels of IL-10 and TNF-a. The absolute numbers of CD3-, CD4-and CD11b-expressing cells in the lesions increased with the progression of infection. The numbers of CD8 cells were reduced in the last phase of infection. The kinetics of T-lymphocyte subsets and the pattern of cytokine expression changed with the type and degree of tissue injury. The small number of Mf with a heavy load of mycobacterial antigens may be the cause of this disturbance in cytokine balance, thus leading to progression of in¯ammation.

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“…Many of these proteins may interact specifically with various parts of the host defence mechanisms, i.e. uptake of mycobacteria into phagocytic and nonphagocytic cells [30], inhibition of phagosome-lysosome fusion [31,32], inhibition of presentation via MHC class I and II [19,33], induction of FAS ligand in phagocytic cells [34], inhibition of production of several cytokines [35] and possibly many more.…”

Section: Protein Secretion and Excretion And The Implications For Thementioning

confidence: 99%

Liberation of Soluble Proteins from Live and Dead Mycobacterial Cells and the Implications for Pathogenicity of Tubercle Bacilli

Wiker¹

2001

Scand J Immunol

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Soluble proteins liberated from live M. tuberculosis are translocated through the cytoplasmic membrane to à periplasmic space'. For further export of proteins across the outer permeability barrier, it is necessary to postulate an excretion mechanism possibly involving some kind of porin. Observations of the repertoire of proteins in culture filtrates after liquid culture of M. tuberculosis show that a large repertoire of various kinds of proteins cross the outer permeability barrier of tubercle bacilli indicating that the excretion mechanism has a wide range of specificities for proteins. Culture filtrates of tubercle bacilli almost always contain both truly secreted proteins and cytoplasmatically-derived proteins. It is questionable whether cytoplasmic proteins can cross an intact cytoplasmic membrane. The simplest explanation for the appearance of cytoplasmic proteins in culture filtrates of tubercle bacilli would be that they are released after disintegration of the cytoplasmic membrane in dying or dead bacilli. Tubercle bacilli armed with secreted factors that may specifically inhibit innate and adaptive immune responses, excrete these from the periplasmic space of live bacilli. Unspecific in its character, the excretion mechanism also liberates proteins that are essential for building and maintaining the cell wall, thereby reducing the effectiveness of this process. This may be part of the explanation why M. tuberculosis and other pathogenic mycobacteria grow so slowly. Finally, it may be postulated that dormant or latent tubercle bacilli use their repertoire of secreted proteins to control their intracellular habitat and that bacterial cytoplasmic proteins would not be liberated from such bacilli. The consequence would be that only immune responses to secreted proteins would be effective for elimination of the dormant stage of infection. In a situation with active infection there will be considerable growth and turnover of bacilli with liberation of all kinds of immunogenic substances from the bacilli. In this situation immunity against cytoplasmic proteins would also be effective and immunity to cytoplasmic proteins should also be effective for control of the reactivation of latent disease because as soon as the bacilli start to grow there will also be a subpopulation of dead bacilli on the arena. THE ENVELOPE OF MYCOBACTERIACompared to many other bacterial genera, the outer permeability barrier of mycobacteria is extremely tight and particularly so for M. tuberculosis [1,2]. This is owing to the unusual structure of the mycobacterial cell wall which is highly impermeable to hydrophilic solutes. Hydrophobic solutes can penetrate the barrier [1]. Antibiotics of the most hydrophobic types for example, are also the most effective drugs against mycobacteria [3,4].Considering the extreme rigidity and impermeability of the outer permeability barrier [5] of M. tuberculosis, it is a paradox that liquid cultures contain excessive amounts of soluble proteins which are much larger than the small solutes referred to...

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Increased Expression of Fas Ligand in Human Tuberculosis and Leprosy Lesions: a Potential Novel Mechanism of Immune Evasion in Mycobacterial Infection

Cited by 62 publications

References 45 publications

Contribution of CD8+ T Cells to Control of Mycobacterium tuberculosis Infection

Contribution of CD8+ T Cells to Control of Mycobacterium tuberculosis Infection

In Situ Expression of Cytokines and Cellular Phenotypes in the Lungs of Mice with Slowly Progressive Primary Tuberculosis

Liberation of Soluble Proteins from Live and Dead Mycobacterial Cells and the Implications for Pathogenicity of Tubercle Bacilli

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