Glucosylceramide Administration as a Vaccination Strategy in Mouse Models of Cryptococcosis

• Published in: PloS one Vol. 11; no. 4; p. e0153853
• Main Authors: Mor, Visesato, Farnoud, Amir M, Singh, Ashutosh, Rella, Antonella, Tanno, Hiromasa, Ishii, Keiko, Kawakami, Kazuyoshi, Sato, Toshiya, Del Poeta, Maurizio
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15.04.2016; Public Library of Science (PLoS)
• Subjects: Analysis; Animal models; Animals; Antibodies; Antibodies - chemistry; Antibody response; Antigens; Biology and Life Sciences; Brain; Candida utilis; Cell cycle; Cell division; Central nervous system; Chemical compounds; Cryptococcosis; Cryptococcosis - prevention & control; Cryptococcus; Cryptococcus neoformans; Cytokines - metabolism; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Fungal infections; Fungal Vaccines - administration & dosage; Fungi; Glucosylceramides - administration & dosage; Health aspects; Immunoglobulins; Immunology; Infections; Laboratories; Lethal dose; Leukocyte Count; Life sciences; Lipids; Liver - microbiology; Liver Function Tests; Lungs; Medicine and Health Sciences; Meningitis; Meningoencephalitis; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred CBA; Opportunist infection; Pharmacology; Physiological aspects; Polysaccharides; Prevention; Proteins; Research and Analysis Methods; Tropical diseases; University graduates; Vaccination; Vaccines; Viral infections; Virulence; Virulence factors; Virulence Factors - chemistry; United States
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0153853

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.