title: Interferon-γ promotes phagocytosis of Cryptococcus neoformans but not Cryptococcus gattii by murine macrophages.
abstract: Among invasive fungal infections, cryptococcosis caused by inhalation of Cryptococcus neoformans or Cryptococcus gattii is particularly dangerous because it can disseminate to the central nervous system and cause life-threatening meningitis or meningoencephalitis. Previous reports described significant differences in the histopathological features of C. neoformans and C. gattii infection, such as greater pathogen proliferation and a limited macrophage response in mouse lung infected by C. gattii. To elucidate the difference in pathogenicity of these two Cryptococcus species, we investigated the interaction of C. neoformans and C. gattii with murine macrophages, the first line of host defense, by confocal laser microscopy. Only thin-capsulated, and not thick-capsulated C. neoformans and C. gattii were phagocytosed by macrophages. Preactivation with interferon-γ increased the phagocytic rate of thin-capsulated C. neoformans up to two-fold, but did not promote phagocytosis of thin-capsulated C. gattii. Lipopolysaccharide preactivation or Aspergillus fumigatus conidia co-incubation had no effect on internalization of thin-capsulated C. neoformans or C. gattii by macrophages. Phagocytosis of live thin-capsulated C. neoformans, but not that of live thin-capsulated C. gattii, induced interleukin-12 release from macrophages. However, phagocytosis of heat-killed or paraformaldehyde-fixed thin-capsulated C. neoformans did not increase IL-12 release, showing that the internalization of live yeast is important for initiating the immune response during C. neoformans-macrophage interactions. Our data suggest that macrophage response to C. gattii is limited compared with that to C. neoformans and that these results may partially explain the limited immune response and the greater pathogenicity of C. gattii.
authors.affiliation: Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan.
authors.forename: Yurika
authors.initials: Y
authors.lastname: Ikeda-Dantsuji
authors.affiliation: Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan; Department of Infectious Diseases and Infection Control, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ohno
authors.affiliation: Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Tanabe
authors.affiliation: Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Umeyama
authors.affiliation: Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Ueno
authors.affiliation: Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Nagi
authors.affiliation: Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamagoe
authors.affiliation: Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kinjo
authors.affiliation: Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan. Electronic address: ym46@niid.go.jp.
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Miyazaki
mesh_terms: D000818:Animals; D002460:Cell Line; D003453:Cryptococcosis / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D056285:Cryptococcus gattii / Q000187:drug effects*; D003455:Cryptococcus neoformans / Q000187:drug effects*; D007371:Interferon-gamma / Q000494:pharmacology*; D018664:Interleukin-12 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000378:metabolism / Q000382:microbiology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects*
chemical_list: D008070:Lipopolysaccharides; D018664:Interleukin-12; D007371:Interferon-gamma
keywords: Cryptococcus gattii; Cryptococcus neoformans; Interferon-γ; Interleukin-12; Macrophage; Phagocytosis