title: Invariant natural killer T cells recognize a fungal glycosphingolipid that can induce airway hyperreactivity.
abstract: Aspergillus fumigatus is a saprophytic fungus that is ubiquitous in the environment and is commonly associated with allergic sensitization and severe asthma in humans. Although A. fumigatus is recognized by multiple microbial pattern-recognition receptors, we found that an A. fumigatus-derived glycosphingolipid, asperamide B, directly activates invariant natural killer T (iNKT) cells in vitro in a CD1d-restricted, MyD88-independent and dectin-1-independent fashion. Moreover, asperamide B, when loaded onto CD1d, directly stained, and was sufficient to activate, human and mouse iNKT cells. In vivo, asperamide B rapidly induced airway hyperreactivity, which is a cardinal feature of asthma, by activating pulmonary iNKT cells in an interleukin-33 (IL-33)-ST2-dependent fashion. Asperamide B is thus the first fungal glycolipid found to directly activate iNKT cells. These results extend the range of microorganisms that can be directly detected by iNKT cells to the kingdom of fungi and may explain how A. fumigatus can induce severe chronic respiratory diseases in humans.
authors.affiliation: 1] Division of Immunology and Allergy, Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA. [2].
authors.forename: Lee A
authors.initials: LA
authors.lastname: Albacker
authors.forename: Vinod
authors.initials: V
authors.lastname: Chaudhary
authors.forename: Ya-Jen
authors.initials: YJ
authors.lastname: Chang
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Chuang
authors.forename: Muriel
authors.initials: M
authors.lastname: Pichavant
authors.forename: Rosemarie H
authors.initials: RH
authors.lastname: DeKruyff
authors.forename: Paul B
authors.initials: PB
authors.lastname: Savage
authors.forename: Dale T
authors.initials: DT
authors.lastname: Umetsu
mesh_terms: D000818:Animals; D001232:Aspergillus fumigatus / Q000737:chemistry*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000276:immunology*; D006028:Glycosphingolipids / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D055611:Natural Killer T-Cells / Q000276:immunology*; D013107:Sphingolipids / Q000633:toxicity
chemical_list: C524749:1-O-beta-D-glucopyranosyl-(2S,2'R,3R,3'E,4E,8E)-N-(2'-hydroxy-3'-hexadecenoyl)-9-methyl-4,8-icosadien-1,3-diol; D006028:Glycosphingolipids; D013107:Sphingolipids