title: Phagosomes induced by cytokines function as anti-Listeria vaccines: novel role for functional compartmentalization of STAT-1 protein and cathepsin-D.
abstract: Phagosomes are critical compartments for innate immunity. However, their role in the protection against murine listeriosis has not been examined. We describe here that listericidal phago-receptosomes are induced by the function of IFN-γ or IL-6 as centralized compartments for innate and adaptive immunity because they are able to confer protection against murine listeriosis. These phago-receptosomes elicited LLO(91-99)/CD8(+)- and LLO(189-201)/CD4(+)-specific immune responses and recruited mature dendritic cells to the vaccination sites controlled by T cells. Moreover, they present exceptional features as efficient vaccine vectors. First, they compartmentalize a novel listericidal STAT-1-mediated signaling pathway that confines multiple innate immune components to the same environment. Second, they show features of MHC class II antigen-loading competent compartments for cathepsin-D-mediated LLO processing. Third, murine cathepsin-D deficiencies fail to develop protective immunity after vaccination with listericidal phago-receptosomes induced by IFN-γ or IL-6. Therefore, it appears that the connection of STAT-1 and cathepsin-D in a single compartment is relevant for protection against listeriosis.
authors.affiliation: Grupo de Genómica, Proteómica de Infecciones Bacterianas e Inflamación, Fundación Marqués de Valdecilla-IFIMAV and Hospital Santa Cruz de Liencres, 39120-Santander, Cantabria, Spain.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Carrasco-Marín
authors.forename: Estela
authors.initials: E
authors.lastname: Rodriguez-Del Rio
authors.forename: Elisabet
authors.initials: E
authors.lastname: Frande-Cabanes
authors.forename: Raquel
authors.initials: R
authors.lastname: Tobes
authors.forename: Eduardo
authors.initials: E
authors.lastname: Pareja
authors.forename: M Jesús
authors.initials: MJ
authors.lastname: Lecea-Cuello
authors.forename: Marta
authors.initials: M
authors.lastname: Ruiz-Sáez
authors.forename: Fidel
authors.initials: F
authors.lastname: Madrazo-Toca
authors.forename: Christoph
authors.initials: C
authors.lastname: Hölscher
authors.forename: Carmen
authors.initials: C
authors.lastname: Alvarez-Dominguez
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002402:Cathepsin D / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008089:Listeria monocytogenes / Q000276:immunology* / Q000378:metabolism; D008088:Listeriosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D051379:Mice; D018345:Mice, Knockout; D010588:Phagosomes / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
chemical_list: D001428:Bacterial Vaccines; D000949:Histocompatibility Antigens Class II; D015850:Interleukin-6; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D007371:Interferon-gamma; D002402:Cathepsin D; C533923:Ctsd protein, mouse