Phagosomes Induced by Cytokines Function as anti-Listeria Vaccines

• 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: Elsevier Inc 27-04-2012
• Subjects: Dendritic Cells; Immunotherapy; Infectious Diseases; Phagocytosis; Vaccines; Infectious Diseases; Dendritic Cells; Vaccines; Immunotherapy; Phagocytosis
• 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.
Background: The effectiveness of phagosomes as vaccines is unknown.
Results: Listericidal phagosomes contain a compartmentalized signaling pathway and a nontoxic listeriolysin form bound to immune molecules. As vaccines they activate effector T cells and recruit immune cells.
Conclusion: Protection with listericidal phagosomes requires recruitment of dendritic cells and T cell regulation.
Significance: Phagosomes are effective immunotherapies and are a new generation of vaccine tools.