title: Sphingosine 1-phosphate induces antimicrobial activity both in vitro and in vivo.
abstract: Sphingosine 1-phosphate (S1P), a polar sphingolipid metabolite, is involved in a wide spectrum of biological processes, including Ca(++) mobilization, cell growth, differentiation, motility, and cytoskeleton organization. Here, we show a novel role of S1P in the induction of antimicrobial activity in human macrophages that leads to the intracellular killing of nonpathogenic Mycobacterium smegmatis and pathogenic M. tuberculosis. Such activity is mediated by host phospholipase D, which favors the acidification of mycobacteria-containing phagosomes. Moreover, when it was intravenously injected in mycobacteria-infected mice, S1P reduced mycobacterial growth and pulmonary tissue damage. These results identify S1P as a novel regulator of the host antimicrobial effector pathways.
authors.affiliation: Department of Biology, University of Tor Vergata, Rome, Italy.
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Garg
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Volpe
authors.forename: Graziana
authors.initials: G
authors.lastname: Palmieri
authors.forename: Maurizio
authors.initials: M
authors.lastname: Mattei
authors.forename: Domenico
authors.initials: D
authors.lastname: Galati
authors.forename: Angelo
authors.initials: A
authors.lastname: Martino
authors.forename: Maria S
authors.initials: MS
authors.lastname: Piccioni
authors.forename: Emanuela
authors.initials: E
authors.lastname: Valente
authors.forename: Elena
authors.initials: E
authors.lastname: Bonanno
authors.forename: Paolo
authors.initials: P
authors.lastname: De Vito
authors.forename: Patrizia M
authors.initials: PM
authors.lastname: Baldini
authors.forename: Luigi G
authors.initials: LG
authors.lastname: Spagnoli
authors.forename: Vittorio
authors.initials: V
authors.lastname: Colizzi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fraziano
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015169:Colony Count, Microbial; D004305:Dose-Response Relationship, Drug; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D008168:Lung / Q000276:immunology / Q000382:microbiology; D008246:Lysophospholipids / Q000276:immunology* / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D018613:Microscopy, Confocal; D020102:Mycobacterium smegmatis / Q000254:growth & development / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology*; D010739:Phospholipase D / Q000276:immunology; D013110:Sphingosine / Q000031:analogs & derivatives / Q000276:immunology* / Q000494:pharmacology*; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D018709:Statistics, Nonparametric; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology
chemical_list: D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D010739:Phospholipase D; D013110:Sphingosine