Cryptococcus neoformans activates bone marrow-derived conventional dendritic cells rather than plasmacytoid dendritic cells and down-regulates macrophages.
Induction of IL-12 and IL-23 is essential for protective immunity against Cryptococcusneoformans. The contribution of dendritic cells vs. macrophages to IL-12/23 production in response to C. neoformans infection is unclear. Activation of conventional bone marrow-derived dendritic cells (BMDC), plasmacytoid BMDC, and bone marrow-derived macrophages (BMMPhi) was assessed by analyzing cytokine responses and the expression of MHC-II, CD86, and CD80 in each cell type. Cryptococcus neoformans induced the release of IL-12/23p40 by BMDC, but not by BMMPhi, in a TLR2- and TLR4-independent but MyD88-dependent manner. Conventional BMDC rather than plasmacytoid BMDC up-regulated MHC-II and CD86, while BMMPhi down-regulated MHC-II and CD86 in response to C. neoformans. The up-regulation of MHC-II and CD86 on BMDC required MyD88. Our data point to conventional DC as critical IL-12/23-producing antigen-presenting cells during cryptococcosis.
Siegemund
Sabine
S
Institute of Immunology, College of Veterinary Medicine, Leipzig, Germany.
Alber
Gottfried
G
D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology*; D003453:Cryptococcosis / Q000276:immunology / Q000473:pathology*; D003455:Cryptococcus neoformans / Q000276:immunology / Q000502:physiology*; D003713:Dendritic Cells / Q000378:metabolism / Q000382:microbiology / Q000502:physiology*; D015536:Down-Regulation; D008264:Macrophages / Q000276:immunology / Q000382:microbiology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL