Siegemund Sabine, Alber Gottfried
Institute of Immunology, College of Veterinary Medicine, Leipzig, Germany.
FEMS Immunol Med Microbiol. 2008 Apr;52(3):417-27. doi: 10.1111/j.1574-695X.2008.00391.x.
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.
诱导IL-12和IL-23对于针对新型隐球菌的保护性免疫至关重要。在新型隐球菌感染后，树突状细胞与巨噬细胞对IL-12/23产生的贡献尚不清楚。通过分析细胞因子反应以及每种细胞类型中MHC-II、CD86和CD80的表达，评估了传统骨髓来源的树突状细胞（BMDC）、浆细胞样BMDC和骨髓来源的巨噬细胞（BMMPhi）的活化情况。新型隐球菌以不依赖TLR2和TLR4但依赖MyD88的方式诱导BMDC释放IL-12/23p40，而BMMPhi则不释放。传统BMDC而非浆细胞样BMDC上调MHC-II和CD86，而BMMPhi在新型隐球菌刺激下下调MHC-II和CD86。BMDC上MHC-II和CD86的上调需要MyD88。我们的数据表明，在隐球菌病期间，传统DC是产生关键IL-12/23的抗原呈递细胞。
