Sphingosine 1-phosphate induces antimicrobial activity both in vitro and in vivo.
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.
Garg
Sanjay K
SK
Department of Biology, University of Tor Vergata, Rome, Italy.
Volpe
Elisabetta
E
Palmieri
Graziana
G
Mattei
Maurizio
M
Galati
Domenico
D
Martino
Angelo
A
Piccioni
Maria S
MS
Valente
Emanuela
E
Bonanno
Elena
E
De Vito
Paolo
P
Baldini
Patrizia M
PM
Spagnoli
Luigi G
LG
Colizzi
Vittorio
V
Fraziano
Maurizio
M
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
D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D010739:Phospholipase D; D013110:Sphingosine