Published online before print June 16, 2003

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(Journal of Leukocyte Biology. 2003;74:370-378.)
© 2003 by Society for Leukocyte Biology

The polysaccharide capsule of Cryptococcus neoformans interferes with human dendritic cell maturation and activation

Anna Vecchiarelli^*,1, Donatella Pietrella^*, Patrizia Lupo^*, Francesco Bistoni^*, Diane C. McFadden and Arturo Casadevall

^* Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy; and
Albert Einstein College of Medicine, Bronx, New York

¹Correspondence: Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, 06122 Perugia, Italy. E-mail: vecchiar{at}unipg.it

The ability of encapsulated and acapsular strains of Cryptococcus neoformans to activate dendritic cells (DC) derived from monocytes stimulated with granulocyte macrophage-colony stimulating factor and interleukin-4 was evaluated. Profound differences in DC response to encapsulated and acapsular C. neoformans strains were observed. In particular, (i) the acapsular strain was easily phagocytosed by immature DC, and the process induced several molecular markers, such as major histocompatibility complex (MHC) class I and class II, CD40, and CD83, which are characteristic of mature DC; (ii) the encapsulated strain did not up-regulate MHC class I and class II and CD83 molecules; (iii) the soluble capsular polysaccharide glucuronoxylomannan (GXM) is unable to regulate MHC class I and class II molecules; (iv) the addition of monoclonal antibody to GXM (anti-GXM) to the encapsulated strain facilitated antigen-presenting cell maturation by promoting ingestion of C. neoformans via Fc receptor for immunoglobulin G (FcR)II (CD32) and FcRIII (CD16); (v) pertubation of FcRII or FcRIII was insufficient to promote DC maturation; and (vi) optimal DC maturation permitted efficient T cell activation and differentiation, as documented by the enhancement of lymphoproliferation and interferon- production. These results indicate that the C. neoformans capsule interferes with DC activation and maturation, indicating a new pathway by which the fungus may avoid an efficient T cell response.

Key Words: GM-CSF • interleukin-4 • major histocompatibility complex • glucuronoxylomannan

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