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Infection and Immunity, February 2005, p. 820-827, Vol. 73, No. 2
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.2.820-827.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Mannoproteins from Cryptococcus neoformans Promote Dendritic Cell Maturation and Activation

Donatella Pietrella,1 Cristina Corbucci,1 Stefano Perito,1 Giovanni Bistoni,2 and Anna Vecchiarelli1*

Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy,1 Biological Sciences, Imperial College London, London, United Kingdom2

Received 30 July 2004/ Returned for modification 31 August 2004/ Accepted 19 October 2004

Our previous data show that mannoproteins (MPs) from Cryptococcus neoformans are able to induce protective responses against both C. neoformans and Candida albicans. Here we provide evidence that MPs foster maturation and activation of human dendritic cells (DCs). Maturation was evaluated by the ability of MPs to facilitate expression of costimulatory molecules such as CD40, CD86, CD83, and major histocompatibility complex classes I and II and to inhibit receptors such as CD14, CD16, and CD32. Activation of DCs was measured by the capacity of MPs to promote interleukin-12 and tumor necrosis factor alpha secretion. DC-induced maturation and interleukin-12 induction are largely mediated by engagement of mannose receptors and presume MP internalization and degradation. DC activation leads to I{kappa}B{alpha} phosphorylation, which is necessary for nuclear factor {kappa}B transmigration into the nucleus. MP-loaded DCs are efficient stimulators of T cells and show a remarkable capacity to promote CD4 and CD8 proliferation. In conclusion, we have evidenced a novel regulatory role of MPs that promotes their candidacy as a vaccine against fungi.

* Corresponding author. Mailing address: Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, 06122 Perugia, Italy. Phone and fax: 39-075-585-7407. E-mail: vecchiar{at}unipg.it.

Editor: T. R. Kozel

Infection and Immunity, February 2005, p. 820-827, Vol. 73, No. 2
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.2.820-827.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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