ABSTRACT
Protection against intracellular pathogens is usually mediated by cytotoxic T lymphocytes (CTL). Induction of a protective CTL response for vaccination purposes has proven difficult because of the limited access of protein antigens or attenuated pathogens to the MHC class I presentation pathway. We show here that pH-sensitive PE/CHEMS liposomes can be used as a vehicle to efficiently deliver intact proteins for presentation by MHC class I. Mice immunized with listerial proteins encapsulated in such liposomes launched a strong CTL response and were protected against a subsequent challenge with L. monocytogenes. Remarkably, the CTL response was induced independently of detectable CD4(+) T cell help.
Subject(s)
Antigens, Bacterial/immunology , Bacterial Proteins/immunology , Liposomes/immunology , Listeria monocytogenes/immunology , Listeriosis/immunology , Listeriosis/prevention & control , Spleen/immunology , T-Lymphocyte Subsets/cytology , T-Lymphocytes, Cytotoxic/cytology , T-Lymphocytes, Helper-Inducer/cytology , Animals , Bacterial Toxins/immunology , Cell Line , Cell Line, Tumor , Cell Proliferation , Cytotoxins/immunology , Heat-Shock Proteins/immunology , Hemolysin Proteins/immunology , Histocompatibility Antigens Class II/genetics , Humans , Immunization , Injections, Intraperitoneal , Mice , Mice, Inbred BALB C , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, KnockoutABSTRACT
An important feature of microbial infections is the ability of the microorganisms to interfere with and modulate the induction of host immune reactions. However, little is known about the effects of broad host range pathogens such as Listeria monocytogenes on similar cell types in different hosts. Here we examine the effects of the human and animal pathogen L. monocytogenes on human dendritic cells (DC) since this type of cells is essential for the initiation of immune responses. Listeria are phagocytosed efficiently by immature human DC and the bacteria escape from the phagolysosome quickly. Lack of the pore-forming activity of listeriolysin, which was found to be essential for the vacuolar escape of this bacterium in other cell types, retarded but did not prevent egress from the vacuole. Treatment of cultures of immature DC with L. monocytogenes resulted in rapid changes in morphology and cellular constitution followed by maturation of the DC. This could be judged by the appearance of maturation-specific cell surface markers. Antigen presentation to CD4 T cells was apparently not impaired by the infection. These results are in clear contrast to results obtained previously in the mouse system (Guzman et al., Mol. Microbiol. 1996. 20: 119 - 126; Darji et al., Eur. J. Immunol. 1997. 27: 1696 - 1703.).
Subject(s)
Antigen Presentation , Bacterial Toxins , Dendritic Cells/microbiology , Dendritic Cells/physiology , Listeria monocytogenes/physiology , Phagosomes/immunology , Heat-Shock Proteins/physiology , Hemolysin Proteins , Histocompatibility Antigens Class II/physiology , Humans , Vacuoles/microbiologyABSTRACT
We have examined the human humoral immune response directed against proteins of Listeria monocytogenes in both healthy individuals and listeriosis patients. Two major targets for an antibody response were found in individuals that did not suffer from listeriosis: listeriolysin (Hly) and the recently described internalin-related protein (IrpA). In contrast, the humoral response in listeriosis patients appears to be more heterogeneous and included Hly, IrpA, InlB, and ActA as major targets.
