Phagosomes induced by cytokines function as anti-Listeria vaccines: novel role for functional compartmentalization of STAT-1 protein and cathepsin-D

• Published in: The Journal of biological chemistry Vol. 287; no. 18; pp. 14310 - 14324
• Main Authors: Carrasco-Marín, Eugenio, Rodriguez-Del Rio, Estela, Frande-Cabanes, Elisabet, Tobes, Raquel, Pareja, Eduardo, Lecea-Cuello, M Jesús, Ruiz-Sáez, Marta, Madrazo-Toca, Fidel, Hölscher, Christoph, Alvarez-Dominguez, Carmen
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 27-04-2012
• Subjects: Animals; Bacterial Vaccines - immunology; Cathepsin D - genetics; Cathepsin D - immunology; Cathepsin D - metabolism; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Dendritic Cells - immunology; Dendritic Cells - metabolism; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - immunology; Histocompatibility Antigens Class II - metabolism; Immunology; Interferon-gamma - genetics; Interferon-gamma - immunology; Interferon-gamma - metabolism; Interleukin-6 - genetics; Interleukin-6 - immunology; Interleukin-6 - metabolism; Listeria monocytogenes - immunology; Listeria monocytogenes - metabolism; Listeriosis - genetics; Listeriosis - immunology; Listeriosis - metabolism; Listeriosis - prevention & control; Mice; Mice, Knockout; Phagosomes - genetics; Phagosomes - immunology; Phagosomes - metabolism; Signal Transduction - genetics; Signal Transduction - immunology; STAT1 Transcription Factor - genetics; STAT1 Transcription Factor - immunology; STAT1 Transcription Factor - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M112.348615

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.