title: In vivo protection provided by a synthetic new alpha-galactosyl ceramide analog against bacterial and viral infections in murine models.
abstract: Alpha-galactosyl ceramide (α-GalCer) has been known to bind to the CD1d receptor on dendritic cells and activate invariant natural killer T (iNKT) cells, which subsequently secrete T-helper-cell 1 (Th1) and Th2 cytokines, which correlate with anti-infection activity and the prevention of autoimmune diseases, respectively. α-GalCer elicits the secretion of these two cytokines nonselectively, and thus, its effectiveness is limited by the opposing effects of the Th1 and Th2 cytokines. Reported here is the synthesis of a new α-GalCer analog (compound C34), based on the structure of CD1d, with a 4-(4-fluorophenoxy) phenyl undecanoyl modification of the N-acyl moiety of α-GalCer. Using several murine bacterial and viral infection models, we demonstrated that C34 has superior antibacterial and antiviral activities in comparison with those of several other Th1-selective glycolipids and that it is most effective by administering it to mice in a prophylactic manner before or shortly after infection.
authors.affiliation: Genomics Research Center, Academia Sinica, Nankang District, Taipei, Taiwan.
authors.forename: Kun-Hsien
authors.initials: KH
authors.lastname: Lin
authors.forename: Jian-Jong
authors.initials: JJ
authors.lastname: Liang
authors.forename: Wen-I
authors.initials: WI
authors.lastname: Huang
authors.forename: Shao-Ying
authors.initials: SY
authors.lastname: Lin-Chu
authors.forename: Ching-Yao
authors.initials: CY
authors.lastname: Su
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Lee
authors.forename: Jia-Tsong
authors.initials: JT
authors.lastname: Jan
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Lin
authors.forename: Yih-Shyun E
authors.initials: YS
authors.lastname: Cheng
authors.forename: Chi-Huey
authors.initials: CH
authors.lastname: Wong
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D005260:Female; D005699:Galactosylceramides / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D020578:Sphingomonas / Q000187:drug effects* / Q000472:pathogenicity; D013211:Staphylococcus aureus / Q000187:drug effects / Q000472:pathogenicity
chemical_list: D000900:Anti-Bacterial Agents; D005699:Galactosylceramides; C493154:alpha-galactosylceramide