Production of tumor necrosis factor alpha in human leukocytes stimulated by Cryptococcus neoformans

Levitz, Stuart M.; Tabuni, Abdulmoneim; Kornfeld, Hardy; Reardon, Christine Campbell; Golenbock, Douglas T.

doi:10.1128/iai.62.5.1975-1981.1994

Cited by 88 publications

(76 citation statements)

References 28 publications

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“…125 The presence of complement is a prerequisite for TNF-a induction. 125,126 Opsonised C. neoformans also provokes the release of TNF-a from DC. 107 The produced TNF-a efficiently supports ingestion of the encapsulated yeast by CR3-bearing macrophages.…”

Section: Complement-mediated Effector Mechanisms In Cryptococcal Infementioning

confidence: 99%

Complement and fungal pathogens: an update

Speth

Rambach

Würzner

et al. 2008

Mycoses

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Fungal infections are a serious complication in immunocompromised patients such as human immunodeficiency virus-infected individuals, patients with organ transplantations or with haematological neoplasia. The lethality of opportunistic fungal infection is high despite a growing arsenal of antimycotic drugs, implying the urgent need for supportive immunological therapies to strengthen the current inefficient antimicrobial defences of the immunocompromised host. Therefore, increasing effort has been directed to investigating the interplay between fungi and the host immunity and thus to find starting points for additional therapeutic approaches. In this article, we review the actual state of the art concerning the role of complement in the pathogenesis of fungal infections. Important aspects include the activation of the complement system by the fungal pathogen, the efficiency of the complement-associated antimicrobial functions and the arsenal of immune evasion strategies applied by the fungi. The twin functions of complement as an interactive player of the innate immunity and at the same time as a modulator of the adaptive immunity make this defence weapon a particularly interesting therapeutic candidate to mobilise a more effective immune response and to strengthen in one fell swoop a broad spectrum of different immune reactions. However, we also mention the 'Yin-Yang' nature of the complement system in fungal infections, as growing evidence assigns to complement a contributory part in the pathogenesis of fungus-induced allergic manifestations.

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Section: Complement-mediated Effector Mechanisms In Cryptococcal Infementioning

confidence: 99%

Complement and fungal pathogens: an update

Speth

Rambach

Würzner

et al. 2008

Mycoses

View full text Add to dashboard Cite

show abstract

“…Human peripheral blood monocytes were prepared from the leucocyte concentrate by Ficoll-hypaque density gradient centrifugation and adherence to culture dishes in serum-free Dulbecco's modi®ed Eagle's minimal essential medium (DMEM). 25 The adherent cells were recovered by scraping and resuspended in RPMI-1640 containing 10% fetal bovine serum (FBS). Cells were preincubated with chloroquine for 2 h before addition of PMA (10 ng/ml).…”

Section: Reagents and Antibodiesmentioning

confidence: 99%

Chloroquine decreases cell‐surface expression of tumour necrosis factor receptors in human histiocytic U‐937 cells

et al. 2002

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SUMMARYProin¯ammatory cytokine tumour necrosis factor (TNF) mediates its diverse effects through cell surface receptors. A variety of in¯ammatory signals are known to modulate TNF activities by changing expression and shedding of cell-surface TNF receptors. We have examined the effects of anti-rheumatic drug chloroquine on the expression of cell surface and soluble TNF receptors in human histiocytic U-937 cells. Chloroquine partially reduced production of soluble p55 and p75 TNF receptors in cells stimulated with phorbol 12-myristate 13-acetate (PMA). In these cells, induction of both TNF receptor mRNA was not changed and the levels of cell-associated TNF receptors were rather increased by chloroquine. Flow cytometric analysis revealed that chloroquine does not inhibit the PMAtriggered shedding of TNF receptors from cell surface, while it was suppressed by a metalloproteinase inhibitor BB-3103. Treatment of U-937 cells with chloroquine signi®cantly reduced the level of cell surface TNF receptors and a similar effect was observed with human peripheral blood monocytes. Other weak-base amines, including hydroxychloroquine, ammonium chloride and methylamine, also induced reduction of cell surface TNF receptors, whereas lysosomal proteinase inhibitor, leupeptin, and BB-3013 were without effect. Our results suggest that chloroquine down-regulates cell surface TNF receptors by retarding their transport to the cell surface, while cleavage of cell surface receptors is not inhibited by chloroquine.

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“…Rather, we found higher initial (day 7) TNF-α concentrations in mice infected with ST5 isolates, suggesting this genotype elicits a more intense initial inflammatory response. Previous studies have suggested that capsule components, or cryptococcal cells themselves, have a dose-dependent ability to stimulate TNF-α production by various immune effector cells 47,48 . The more robust initial inflammatory response we observed may have been due to the ST5 capsular phenotype.…”

Section: Discussionmentioning

confidence: 99%