The intact structural form of LLO in endosomes cannot protect against listeriosis |
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Authors: | Estela Rodriguez-Del Rio Elisabet Frande-Cabanes Raquel Tobes Eduardo Pareja M Jesús Lecea-Cuello Marta Ruiz-Sáez Eugenio Carrasco-Marín Carmen Alvarez-Dominguez |
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Institution: | 1.Grupo de Genómica, Proteómica de Infecciones Bacterianas e Inflamación, Fundación Marqués de Valdecilla-IFIMAV and Hospital Santa Cruz de Liencres (HUMV). Santander. Cantabria, Spain;2.Bioinformatics Unit, Era7 Information Technologies SL, BIC Granada CEEI, Parque Tecnológico de Ciencias de la Salud-Armilla. 18100-Granada, Spain |
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Abstract: | LLO is the major immuno-dominant antigen in listeriosis and is also required for protective immunity. Two forms of LLO can be observed in endosomal membranes, a LLO intact form and a Ctsd-processed LLO1-491 form. Endosomes obtained from resting macrophages contained only LLO intact forms, while endosomes obtained from IFN-activated macrophages contained both forms. Both types of endosomes elicited LLO90-91/CD8+ and LLO189-201/CD4+ specific immune responses. However, only endosomes containing the Ctsd-processed LLO1-491 form showed significant CD4+ and CD8+ T cell responses similar to LM infected bone marrow derived macrophages and characteristic of protective Listeria immunity. Moreover, endosomes with intact LLO could not confer protection as vaccine carriers against murine listeriosis. While endosomes with Ctsd-processed LLO1-491 form showed a moderate ability, slightly lower than high efficiency vaccine vectors as MØ infected with LM. These studies argue that all cell-free membrane vesicles might serve as valid vaccine carriers against infectious agents. Exclusively those cell-free vesicles MIIC competent for LLO processing are protective vaccines vectors since they recruit significant numbers of mature dendritic cells to the vaccination sites and contain a LLO1-491 form that might be accessible for MHC class I and class II antigen presentation. |
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Keywords: | LLO structural forms listeriosis endosomes vaccines |
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