title: Membrane microdomains in immunity: glycosphingolipid-enriched domain-mediated innate immune responses.
abstract: Over the last 30 years, many studies have indicated that glycosphingolipids (GSLs) expressed on the cell surface may act as binding sites for microorganisms. Based on their physicochemical characteristics, GSLs form membrane microdomains with cholesterol, sphingomyelin, glycosylphosphatidylinositol (GPI)-anchored proteins, and various signaling molecules, and GSL-enriched domains have been shown to be involved in these defense responses. Among the GSLs, lactosylceramide (LacCer, CDw17) can bind to various microorganisms. LacCer is expressed at high levels on the plasma membrane of human neutrophils, and forms membrane microdomains associated with the Src family tyrosine kinase Lyn. LacCer-enriched membrane microdomains mediate superoxide generation, chemotaxis, and non-opsonic phagocytosis. Therefore, LacCer-enriched membrane microdomains are thought to function as pattern recognition receptors (PRRs) to recognize pathogen-associated molecular patterns (PAMPs) expressed on microorganisms. In contrast, several pathogens have developed infection mechanisms using membrane microdomains. In addition, some pathogens have the ability to avoid degradation by escaping from the vacuolar compartment or preventing phagosome maturation, utilizing membrane microdomains, such as LacCer-enriched domains, of host cells. The detailed molecular mechanisms of these membrane microdomain-associated host-pathogen interactions remain to be elucidated.
authors.affiliation: Institute for Environmental and Gender-specific Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan. iwabuchi@juntendo.ac.jp
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Iwabuchi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nakayama
authors.forename: Hiromi
authors.initials: H
authors.lastname: Masuda
authors.forename: Katsunari
authors.initials: K
authors.lastname: Kina
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Takamori
mesh_terms: D000818:Animals; D006028:Glycosphingolipids / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D007790:Lactosylceramides / Q000378:metabolism / Q000502:physiology; D021962:Membrane Microdomains / Q000502:physiology*; D010587:Phagocytosis; D051192:Receptors, Pattern Recognition / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D006028:Glycosphingolipids; D007790:Lactosylceramides; D051192:Receptors, Pattern Recognition; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases