title: Role of sphingosine-1-phosphate (S1P) and S1P receptor 2 in the phagocytosis of Cryptococcus neoformans by alveolar macrophages.
abstract: The pathogenic fungus Cryptococcus neoformans is a major cause of morbidity and mortality in immunocompromised individuals. Infection of the human host occurs through inhalation of infectious propagules following environmental exposure. In the lung, C. neoformans can reside in the extracellular environment of the alveolar spaces or, upon phagocytosis, it can survive and grow intracellularly within alveolar macrophages (AMs). In previous studies, we found that sphingosine kinase 1 (SK1) influenced the intracellular residency of C. neoformans within AMs. Therefore, with this study we aimed to examine the role of the SK1 lipid product, sphingosine-1-phosphate (S1P), in the AMs-C. neoformans interaction. It was found that extracellular S1P enhances the phagocytosis of C. neoformans by AMs. Using both genetic and pharmacological approaches we further show that extracellular S1P exerts its effect on the phagocytosis of C. neoformans by AMs through S1P receptor 2 (S1P2). Interestingly, loss of S1P2 caused a dramatic decrease in the mRNA levels of Fcγ receptors I (FcγRI), -II and -III. In conclusion, our data suggest that extracellular S1P increases antibody-mediated phagocytosis through S1P2 by regulating the expression of the phagocytic Fcγ receptors.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Travis
authors.initials: T
authors.lastname: McQuiston
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Chiara
authors.initials: C
authors.lastname: Luberto
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.|Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA.|Division of Infectious Diseases, Medical University of South Carolina, Charleston, SC, USA.|Department of Craniofacial Biology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Del Poeta
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003453:Cryptococcosis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000235:genetics / Q000276:immunology*; D005260:Female; D005656:Fungal Proteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008246:Lysophospholipids / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010587:Phagocytosis; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology; D049349:Receptors, Lysosphingolipid / Q000235:genetics / Q000276:immunology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000276:immunology
chemical_list: D005656:Fungal Proteins; D008246:Lysophospholipids; D017452:Receptors, IgG; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D013110:Sphingosine