The polysaccharide capsule of Cryptococcus neoformans interferes with human dendritic cell maturation and activation.
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 (FcgammaR)II (CD32) and FcgammaRIII (CD16); (v) pertubation of FcRgammaII or FcgammaRIII 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-gamma 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.
Vecchiarelli
Anna
A
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy. vecchiar@unipg.it
Pietrella
Donatella
D
Lupo
Patrizia
P
Bistoni
Francesco
F
McFadden
Diane C
DC
Casadevall
Arturo
A
D002455:Cell Division; D003453:Cryptococcosis; D003455:Cryptococcus neoformans / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D016753:Interleukin-10 / Q000502:physiology; D008213:Lymphocyte Activation; D009000:Monocytes / Q000502:physiology*; D010587:Phagocytosis; D011134:Polysaccharides / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D011134:Polysaccharides; D017452:Receptors, IgG; D016753:Interleukin-10; C027478:glucuronoxylomannan; D007371:Interferon-gamma