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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bacterial Vaccines / immunology*
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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Cathepsin D / genetics
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Cathepsin D / immunology*
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Cathepsin D / metabolism
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Dendritic Cells / immunology
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Dendritic Cells / metabolism*
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Histocompatibility Antigens Class II / genetics
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Histocompatibility Antigens Class II / immunology
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Histocompatibility Antigens Class II / metabolism
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Interferon-gamma / genetics
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Interferon-gamma / immunology*
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Interferon-gamma / metabolism
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Interleukin-6 / genetics
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Interleukin-6 / immunology*
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Interleukin-6 / metabolism
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Listeria monocytogenes / immunology*
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Listeria monocytogenes / metabolism
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Listeriosis / genetics
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Listeriosis / immunology*
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Listeriosis / metabolism
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Listeriosis / prevention & control
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Mice
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Mice, Knockout
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Phagosomes / genetics
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Phagosomes / immunology*
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Phagosomes / metabolism
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STAT1 Transcription Factor / genetics
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STAT1 Transcription Factor / immunology*
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STAT1 Transcription Factor / metabolism
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Signal Transduction / genetics
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Signal Transduction / immunology
Substances
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Bacterial Vaccines
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Histocompatibility Antigens Class II
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Interleukin-6
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STAT1 Transcription Factor
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Stat1 protein, mouse
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Interferon-gamma
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Cathepsin D
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Ctsd protein, mouse