This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Murphy, J. W. Articles by Wong, S. C. Search for Related Content PubMed PubMed Citation Articles by Murphy, J. W. Articles by Wong, S. C.

 Previous Article  |  Next Article 

Infect. Immun., Nov 1997, 4564-4571, Vol 65, No. 11
Copyright © 1997, American Society for Microbiology

Direct interactions of human natural killer cells with Cryptococcus neoformans inhibit granulocyte-macrophage colony-stimulating factor and tumor necrosis factor alpha production

JW Murphy, A Zhou and SC Wong
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA. juneann- murphy@uokhsc.edu

Human natural killer (NK) cells and T lymphocytes can bind to and inhibit the growth of the yeast-like organism Cryptococcus neoformans. Binding of target cells to NK or T cells also has the potential to modulate cytokine production by the effector cells. In this study, we assessed the ability of C. neoformans to modulate NK cell production, or in some cases T-cell production, of granulocyte-macrophage colony- stimulating factor (GM-CSF) or tumor necrosis factor alpha (TNF-alpha). We found that freshly isolated human NK cells from most individuals make GM-CSF and TNF-alpha constitutively when cultured in vitro. The addition of C. neoformans to T-cell fractions which do not make GM-CSF constitutively did not affect GM-CSF production, but the addition of C. neoformans to NK cell fractions significantly reduced the amounts of GM- CSF produced in most NK cell samples. The reduction in the amount of GM- CSF in C. neoformans-NK cell cocultures could not be attributed to loss of lymphocyte viability or to C. neoformans adsorbing or degrading the cytokine and was dependent on direct contact between the NK cells and cryptococcal cells. GM-CSF was not the only cytokine to be down- regulated. TNF-alpha production was also diminished when NK cells were incubated with C. neoformans. The regulation of both cytokines was at the transcriptional level because GM-CSF and TNF-alpha mRNA levels were lower in NK cell samples incubated with C. neoformans than in NK cell samples incubated without C. neoformans. Diminished production of constitutively produced cytokines resulting from the interaction of NK cells with cryptococcal cells has the potential to affect phagocytic cells in the immediate regional environment and to damp the immune response.

This article has been cited by other articles:

• Herring, A. C., Falkowski, N. R., Chen, G.-H., McDonald, R. A., Toews, G. B., Huffnagle, G. B. (2005). Transient Neutralization of Tumor Necrosis Factor Alpha Can Produce a Chronic Fungal Infection in an Immunocompetent Host: Potential Role of Immature Dendritic Cells. Infect. Immun. 73: 39-49 [Abstract] [Full Text]  
• Herring, A. C., Lee, J., McDonald, R. A., Toews, G. B., Huffnagle, G. B. (2002). Induction of Interleukin-12 and Gamma Interferon Requires Tumor Necrosis Factor Alpha for Protective T1-Cell-Mediated Immunity to Pulmonary Cryptococcus neoformans Infection. Infect. Immun. 70: 2959-2964 [Abstract] [Full Text]  
• Mozaffarian, N., Casadevall, A., Berman, J. W. (2000). Inhibition of Human Endothelial Cell Chemokine Production by the Opportunistic Fungal Pathogen Cryptococcus neoformans. J. Immunol. 165: 1541-1547 [Abstract] [Full Text]