title: Glucosylceramide Administration as a Vaccination Strategy in Mouse Models of Cryptococcosis.
abstract: Cryptococcus neoformans is an opportunistic fungal pathogen and the causative agent of the disease cryptococcosis. Cryptococcosis is initiated as a pulmonary infection and in conditions of immune deficiency disseminates to the blood stream and central nervous system, resulting in life-threatening meningoencephalitis. A number of studies have focused on the development of a vaccine against Cryptococcus, primarily utilizing protein-conjugated components of the Cryptococcus polysaccharide capsule as antigen. However, there is currently no vaccine against Cryptococcus in the clinic. Previous studies have shown that the glycosphingolipid, glucosylceramide (GlcCer), is a virulence factor in C. neoformans and antibodies against this lipid inhibit fungal growth and cell division. In the present study, we have investigated the possibility of using GlcCer as a therapeutic agent against C. neoformans infections in mouse models of cryptococcosis. GlcCer purified from a non-pathogenic fungus, Candida utilis, was administered intraperitoneally, prior to infecting mice with a lethal dose of C. neoformans. GlcCer administration prevented the dissemination of C. neoformans from the lungs to the brain and led to 60% mouse survival. GlcCer administration did not cause hepatic injury and elicited an anti-GlcCer antibody response, which was observed independent of the route of administration and the strains of mouse. Taken together, our results suggest that fungal GlcCer can protect mice against lethal doses of C. neoformans infection and can provide a viable vaccination strategy against Cryptococcus.
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, 145 Life Sciences Building, Stony Brook, NY, 11794, United States of America.
authors.forename: Visesato
authors.initials: V
authors.lastname: Mor
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, 145 Life Sciences Building, Stony Brook, NY, 11794, United States of America.
authors.forename: Amir M
authors.initials: AM
authors.lastname: Farnoud
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, 145 Life Sciences Building, Stony Brook, NY, 11794, United States of America.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, 145 Life Sciences Building, Stony Brook, NY, 11794, United States of America.
authors.forename: Antonella
authors.initials: A
authors.lastname: Rella
authors.affiliation: Department of Science of Nursing Practice, Tohoku University Graduate School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai, Miyagi, 980-8575, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Tanno
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai, Miyagi, 980-8575, 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, 2-1 Seiryo-cho, Aoba-ku, Sendai, Miyagi, 980-8575, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawakami
authors.affiliation: Kohjin Life Sciences Co., Ltd. 1-3 Yurakucho 1-Chome.Chiyoda-KU, Tokyo, 100-0006, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, 145 Life Sciences Building, Stony Brook, NY, 11794, United States of America.|Veterans Administration Medical Center, Northport, NY, 11768, United States of America.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Del Poeta
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry; D003453:Cryptococcosis / Q000517:prevention & control*; D003455:Cryptococcus neoformans; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005657:Fungal Vaccines / Q000008:administration & dosage*; D005963:Glucosylceramides / Q000008:administration & dosage*; D007958:Leukocyte Count; D008099:Liver / Q000382:microbiology; D008111:Liver Function Tests; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D014611:Vaccination; D037521:Virulence Factors / Q000737:chemistry
chemical_list: D000906:Antibodies; D016207:Cytokines; D005657:Fungal Vaccines; D005963:Glucosylceramides; D037521:Virulence Factors