Tumor Necrosis Factor (TNF) Induction from Monocyte/Macrophages by Candida Species

Aybay, Cemalettin; İmir, Turgut

doi:10.1016/s0171-2985(96)80059-3

Cited by 25 publications

(23 citation statements)

References 42 publications

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“…These findings agree with earlier reports (3,6,10,18). Production of these cytokines under the influence of C. albicans may enhance acute inflammatory cell influx into infected tissues, activate leukocytes, and promote early noncognate elimination of the organism prior to the development and/or mobilization of an adaptive specific immune response (30,38).…”

Section: Discussionsupporting

confidence: 94%

Candida albicansandCandida kruseiDifferentially Induce Human Blood Mononuclear Cell Interleukin-12 and Gamma Interferon Production

Jingbo

Kang

et al. 2000

Infect Immun

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Protection against Candida infection involves both innate and acquired immune responses, and cytokines produced by monocytes during the innate response may modify the acquired immune response by T cells. We hypothesized that Candida species which differ in pathogenicity can differentially induce production of immunoregulatory cytokines by human monocytes, which in turn modify T cells for immune responses to Candida. To test this hypothesis, we examined the effects of Candida albicans and Candida krusei on immunoregulatory cytokine production by human monocytes and gamma interferon (IFN-␥) production by peripheral blood mononuclear cells (PBMC). Purified monocytes were incubated with live or heat-killed strains of C. albicans and C. krusei at the optimal Candida/monocyte ratio of 0.5. Cytokines in the supernatants were measured by enzyme-linked immunosorbent assay. Our data demonstrated that live C. albicans and C. krusei significantly induced interleukin-10 (IL-10), monocyte chemotactic factor 1, IL-1␤, and tumor necrosis factor alpha production by monocytes relative to unstimulated monocytes. In contrast, unlike C. krusei, pathogenic live strains of C. albicans induced no or only a minimal level of IL-12. The expression of IL-12 p40 mRNA levels by reverse transcription-PCR corroborated the IL-12 protein (p70) findings. In human PBMC, human blood monocytes were the major source of both IL-10 and IL-12 production in response to C. albicans and C. krusei. Upon activation of T cells in the presence of Candida-modified monocytes and antigen-presenting cells, IL-12 production by PBMC treated with Candida organisms correlated strongly with the level of IFN-␥ production by T cells. These results indicate that the virulence of C. albicans may be related to its ability to induce the monocytic type II cytokine IL-10, with a selective inhibition of IL-12 production, which may be responsible for the observed lack of T-cell IFN-␥ and may restrain an effective type I immune response to Candida.

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Section: Discussionsupporting

confidence: 94%

Candida albicansandCandida kruseiDifferentially Induce Human Blood Mononuclear Cell Interleukin-12 and Gamma Interferon Production

Jingbo

Kang

et al. 2000

Infect Immun

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“…All of these cytokines were produced considerably less by C. glabrata-infected MDMs, in comparison with MDMs coincubated with S. cerevisiae or C. albicans. This is in agreement with a study of Aybay and Imir (56), which showed a reduced potency of C. glabrata to induce TNF-a from peritoneal macrophages when compared with various Candida species and S. cerevisiae. Furthermore, IL-10, an anti-inflammatory cytokine that inhibits the secretion of proinflammatory cytokines, was also not induced, suggestive of a generally low stimulation of MDMs by C. glabrata.…”

Section: Discussionsupporting

confidence: 92%

The Facultative Intracellular Pathogen Candida glabrata Subverts Macrophage Cytokine Production and Phagolysosome Maturation

Seider

Brunke

Schild

et al. 2011

The Journal of Immunology

188

226

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Although Candida glabrata is an important human pathogenic yeast, its pathogenicity mechanisms are largely unknown. Immune evasion strategies seem to play key roles during infection, since very little inflammation is observed in mouse models. Furthermore, C. glabrata multiplies intracellularly after engulfment by macrophages. In this study, we sought to identify the strategies that enable C. glabrata to survive phagosome biogenesis and antimicrobial activities within human monocyte-derived macrophages. We show that, despite significant intracellular proliferation, macrophage damage or apoptosis was not apparent, and production of reactive oxygen species was inhibited. Additionally, with the exception of GM-CSF, levels of pro- and anti-inflammatory cytokines were only marginally increased. We demonstrate that adhesion to and internalization by macrophages occur within minutes, and recruitment of endosomal early endosomal Ag 1 and lysosomal-associated membrane protein 1 indicates phagosome maturation. However, phagosomes containing viable C. glabrata, but not heat-killed yeasts, failed to recruit cathepsin D and were only weakly acidified. This inhibition of acidification did not require fungal viability, but it had a heat-sensitive surface attribute. Therefore, C. glabrata modifies the phagosome into a nonacidified environment and multiplies until the host cells finally lyse and release the fungi. Our results suggest persistence of C. glabrata within macrophages as a possible immune evasion strategy.

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“…It is known that both blastospores of C. albicans and killed organisms are able to stimulate monocytes to release proinflammatory cytokines (1,14,35). Therefore, the finding that the killed organisms and live, nongerminating mutants did not stimulate endothelial cells strongly suggests that the TNF-␣ in the medium was produced by the endothelial cells and not by any contaminating monocytes.…”

Section: Discussionmentioning

confidence: 99%

“…The large number of patients at risk for this infection include cancer patients with neutropenia, lowbirth-weight infants, and individuals who have had recent intra-abdominal surgery or extensive burns (1). The use of indwelling central venous catheters and treatment with broadspectrum antibiotics are additional risk factors for this infection.…”

mentioning

confidence: 99%

Mechanisms of the Proinflammatory Response of Endothelial Cells toCandida albicansInfection

Orozco¹,

Zhou²,

Filler

2000

Infect Immun

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Endothelial cells can influence significantly the host inflammatory response against blood-borne microbial pathogens. Previously, we found that endothelial cells respond to in vitro infection with Candida albicans by secreting interleukin 8 (IL-8) and expressing E-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1). We have now examined the mechanisms mediating this endothelial cell response. We determined that C. albicans stimulated endothelial cells to synthesize tumor necrosis factor alpha (TNF-␣), which in turn induced these infected cells to secrete IL-8 and express E-selectin by an autocrine mechanism. Expression of VCAM-1 was mediated not only by TNF-␣ but also by IL-1␣ and IL-1␤, all of which were synthesized by endothelial cells in response to C. albicans. These three cytokines remained primarily cell associated rather than being secreted. Candidal induction of ICAM-1 expression was independent of TNF-␣, IL-1␣, and IL-1␤. These observations demonstrate that different proinflammatory endothelial cell responses to C. albicans are induced by distinct mechanisms. A clear understanding of these mechanisms is important for therapeutically modulating the endothelial cell response to C. albicans and perhaps other opportunistic pathogens that disseminate hematogenously.

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Tumor Necrosis Factor (TNF) Induction from Monocyte/Macrophages by Candida Species

Cited by 25 publications

References 42 publications

Candida albicansandCandida kruseiDifferentially Induce Human Blood Mononuclear Cell Interleukin-12 and Gamma Interferon Production

Candida albicansandCandida kruseiDifferentially Induce Human Blood Mononuclear Cell Interleukin-12 and Gamma Interferon Production

The Facultative Intracellular Pathogen Candida glabrata Subverts Macrophage Cytokine Production and Phagolysosome Maturation

Mechanisms of the Proinflammatory Response of Endothelial Cells toCandida albicansInfection

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