TY - JOUR
T1 - The polysaccharide capsule of Cryptococcus neoformans interferes with human dendritic cell maturation and activation
AU - Vecchiarelli, Anna
AU - Pietrella, Donatella
AU - Lupo, Patrizia
AU - Bistoni, Francesco
AU - McFadden, Diane C.
AU - Casadevall, Arturo
PY - 2003/9
Y1 - 2003/9
N2 - 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 (FcγR)II (CD32) and FcγRIII (CD16) ; (v) pertubation of FcRγII or FcγRIII 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-γ 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.
AB - 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 (FcγR)II (CD32) and FcγRIII (CD16) ; (v) pertubation of FcRγII or FcγRIII 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-γ 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.
KW - GM-CSF
KW - Glucuronoxylomannan
KW - Interleukin-4
KW - Major histocompatibility complex
UR - http://www.scopus.com/inward/record.url?scp=0142061503&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0142061503&partnerID=8YFLogxK
U2 - 10.1189/jlb.1002476
DO - 10.1189/jlb.1002476
M3 - Article
C2 - 12949240
AN - SCOPUS:0142061503
VL - 74
SP - 370
EP - 378
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 3
ER -