title: Cryptococcus neoformans Infection in Mice Lacking Type I Interferon Signaling Leads to Increased Fungal Clearance and IL-4-Dependent Mucin Production in the Lungs.
abstract: Type I interferons (IFNs) are secreted by many cell types upon stimulation via pattern recognition receptors and bind to IFN-α/β receptor (IFNAR), which is composed of IFNAR1 and IFNAR2. Although type I IFNs are well known as anti-viral cytokines, limited information is available on their role during fungal infection. In the present study, we addressed this issue by examining the effect of IFNAR1 defects on the host defense response to Cryptococcus neoformans. In IFNAR1KO mice, the number of live colonies was lower and the host immune response mediated not only by Th1 but also by Th2 and Th17-related cytokines was more accelerated in the infected lungs than in WT mice. In addition, mucin production by bronchoepithelial cells and expression of MUC5AC, a major core protein of mucin in the lungs, were significantly higher in IFNAR1KO mice than in WT mice. This increase in mucin and MUC5AC production was significantly inhibited by treatment with neutralizing anti-IL-4 mAb. In contrast, administration of recombinant IFN-αA/D significantly suppressed the production of IL-4, but not of IFN-γ and IL-17A, in the lungs of WT mice after cryptococcal infection. These results indicate that defects of IFNAR1 led to improved clearance of infection with C. neoformans and enhanced synthesis of IFN-γ and the IL-4-dependent production of mucin. They also suggest that type I IFNs may be involved in the negative regulation of early host defense to this infection.
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Ko
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Nomura
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Ikumi
authors.initials: I
authors.lastname: Matsumoto
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Miyasaka
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Tong
authors.initials: T
authors.lastname: Zong
authors.affiliation: Department of Science of Nursing Practice, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Kanno
authors.affiliation: Louis Pasteur Center for Medical Research, Kyoto, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Uno
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Ishii
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawakami
mesh_terms: D000818:Animals; D003453:Cryptococcosis / Q000378:metabolism*; D007370:Interferon Type I / Q000378:metabolism*; D015847:Interleukin-4 / Q000502:physiology*; D008168:Lung / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009077:Mucins / Q000096:biosynthesis*; D053633:Receptor, Interferon alpha-beta / Q000235:genetics; D015398:Signal Transduction
chemical_list: C508032:Ifnar1 protein, mouse; D007370:Interferon Type I; D009077:Mucins; D053633:Receptor, Interferon alpha-beta; D015847:Interleukin-4