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Infection and Immunity, April 2008, p. 1581-1589, Vol. 76, No. 4
0019-9567/08/$08.00+0     doi:10.1128/IAI.01184-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The Presence of Capsule in Cryptococcus neoformans Influences the Gene Expression Profile in Dendritic Cells during Interaction with the Fungus{triangledown} ,{dagger}

P. Lupo,1,3 Y. C. Chang,1 B. L. Kelsall,2 J. M. Farber,2 D. Pietrella,3 A. Vecchiarelli,3 F. Leon,2,{ddagger} and K. J. Kwon-Chung1*

Laboratory of Clinical Investigation,1 Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health Bethesda, Maryland 20892,2 Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, 06123 Perugia, Italy3

Received 28 August 2007/ Returned for modification 9 September 2007/ Accepted 28 January 2008

The aim of this investigation was to study the effect of polysaccharide capsule on the gene expression in dendritic cells (DC) during their interaction with Cryptococcus neoformans. To this end, we used an encapsulated virulent strain of C. neoformans and a cap59 gene-disrupted acapsular avirulent strain derived from the same genetic background. DC were exposed to encapsulated and acapsular C. neoformans strains for 4 h and 18 h, and their transcriptional profiles were analyzed using the Affymetrix mouse gene chip U74Av2. A large number of DC genes were up-regulated after treatment with the acapsular strain. In particular, we observed the up-regulation of the genes involved in DC maturation, such as cell surface receptors, cytokines, and chemokines (interleukin-12 [IL-12], IL-2, IL-1{alpha}, IL-1β, IL-6, IL-10, tumor necrosis factor alpha, CCR7, CCL17, CCL22, CCL3, CCL4, CCL7, and CXCL10), membrane proteins, and the genes involved in antigen processing and presentation as well as cell cycle or apoptosis. The chemokine gene expression data were confirmed by real-time reverse transcription-PCR, while the expression of cytokine genes was correlated with their secretion. A completely different pattern of gene expression was observed for DC treated with an encapsulated strain of C. neoformans. In particular, no significant induction was observed in the expression of the genes mentioned above. Moreover, a number of genes, such as those coding for chemokines, were down-regulated. These results suggest that the polysaccharide capsule shrouding the cell wall of C. neoformans plays a fundamental role in inducing DC response, highlighting the molecular basis of the true nature of immune silencing exerted by capsular material.

* Corresponding author. Mailing address: LCID, NIAID, Bldg. 10, Rm. 11N234, National Institutes of Health, Bethesda, MD 20892. Phone: (301) 496-1602. Fax: (301) 480-3240. E-mail: June_Kwon-Chung{at}nih.gov

{triangledown} Published ahead of print on 4 February 2008.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: A. Casadevall

{ddagger} Present address: Clinical Development, Inflammatory Diseases, MedImmune, One MedImmune Way, Gaithersburg, MD 20878.

Infection and Immunity, April 2008, p. 1581-1589, Vol. 76, No. 4
0019-9567/08/$08.00+0     doi:10.1128/IAI.01184-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Osterholzer, J. J., Milam, J. E., Chen, G.-H., Toews, G. B., Huffnagle, G. B., Olszewski, M. A. (2009). Role of Dendritic Cells and Alveolar Macrophages in Regulating Early Host Defense against Pulmonary Infection with Cryptococcus neoformans. Infect. Immun. 77: 3749-3758 [Abstract] [Full Text]  


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