title: Cryptococcus neoformans suppresses the activation of bone marrow-derived dendritic cells stimulated with its own DNA, but not with DNA from other fungi.
abstract: DNA from Cryptococcus neoformans activates bone marrow-derived dendritic cells (BM-DCs) in a TLR9-dependent manner. In this study, we examined the effect of the culture supernatants of C. neoformans on the activation of BM-DCs caused by its own DNA. C. neoformans supernatants suppressed IL-12p40, IL-6 production and CD40 expression by BM-DCs stimulated with its own DNA, but not with CpG-ODN and DNA from Candida albicans, Saccharomyces cerevisiae or Escherichia coli. In a confocal microscopic analysis, C. neoformans DNA was colocalized with LAMP-1, a late endosomal marker, and TLR9. The culture supernatants did not show any apparent suppression of these responses. In a luciferase reporter assay, C. neoformans supernatants inhibited NFκB activation caused by its own DNA. These inhibitory activities were attenuated by treatment with heat or trypsin. These results indicate that C. neoformans secrete certain proteinous molecules that suppress the activation of BM-DCs caused by its own DNA.
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Abe
authors.forename: Akiko
authors.initials: A
authors.lastname: Miyazato
authors.forename: Daiki
authors.initials: D
authors.lastname: Tanno
authors.forename: Misuzu
authors.initials: M
authors.lastname: Tanaka
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Miyasaka
authors.forename: Keiko
authors.initials: K
authors.lastname: Ishii
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawakami
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology*; D019013:CD40 Antigens / Q000037:antagonists & inhibitors / Q000378:metabolism; D002176:Candida albicans / Q000276:immunology; D003455:Cryptococcus neoformans / Q000276:immunology* / Q000472:pathogenicity*; D004271:DNA, Fungal / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology*; D004926:Escherichia coli / Q000276:immunology; D007108:Immune Tolerance; D053762:Interleukin-12 Subunit p40 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012441:Saccharomyces cerevisiae / Q000276:immunology; D000093242:Interleukin-6 Inhibitors
chemical_list: D019013:CD40 Antigens; D004271:DNA, Fungal; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6; D000093242:Interleukin-6 Inhibitors