GITR contributes to the systemic adjuvanticity of the Escherichia coli heat-labile enterotoxin
| Autor: | Rino Rappuoli, Giuseppe Del Giudice, Jorge Postigo, Carlo Riccardi, Marcos Iglesias, Ramón Merino, J. González, Esther Tamayo, Maigualida Tamara Fernández-Rey, Jesús Merino, Inés Santiuste |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
CD4-Positive T-Lymphocytes
medicine.medical_treatment Bacterial Toxins Immunology Mutant T cells Cell Separation Receptors Nerve Growth Factor Enterotoxin Heat-labile enterotoxin Biology Lymphocyte Activation medicine.disease_cause BELLS-PALSY DENDRITIC CELLS Receptors Tumor Necrosis Factor Enterotoxins Mice Adjuvants Immunologic T-LYMPHOCYTES Costimulation Vaccination ADP-RIBOSYLTRANSFERASE ACTIVITY GENETICALLY DETOXIFIED MUTANTS CHOLERA-TOXIN MUCOSAL ADJUVANTICITY B SUBUNIT IN-VIVO INDUCTION Glucocorticoid-Induced TNFR-Related Protein Adjuvanticity medicine Animals Immunology and Allergy Immunity Mucosal Escherichia coli Mice Knockout chemistry.chemical_classification Mice Inbred BALB C Reverse Transcriptase Polymerase Chain Reaction Escherichia coli Proteins Flow Cytometry Antibodies Bacterial Enzyme chemistry Systemic administration Adjuvant |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 2008-0204 |
| Popis: | El pdf del artículo es el manuscrito de autor.-- et al. The Escherichia coli heat-labile enterotoxin (LT) possesses a powerful mucosal and systemic adjuvant effect. However, little is known about the cellular and molecular basis of the immunostimulatory activity of LT at the mucosal level, and even less information is available on the mechanisms underlying its systemic adjuvant activity. In this study, we show that distinct mechanisms are responsible for the parenteral and mucosal adjuvanticity of LT. Indeed, the systemic administration of LT upregulates the expression of glucocorticoid-induced TNFR-related protein (GITR), but not other activation markers, in naive T cells. Using WT and GITR-deficient mice and LT and its enzymatically inactive mutant LTK63 as adjuvants, we show that the induction of GITR expression in T cells accounts for the systemic immunostimulatory capacity of LT, which requires an intact enzymatic activity. In contrast, the mucosal administration of LT does not induce GITR expression on Peyer's patche T cells and accordingly no differences are observed in the mucosal adjuvanticity of LT between WT and GITR-deficient mice. Altogether, our results demonstrate the distinct effect of LT after parenteral administration when compared with the mucosal delivery, and describe a new mechanism of LT adjuvanticity related to its ability to induce the expression of GITR in CD4+ T cells. This work was supported by grants from the Ministerio de Educación y Ciencia, Spain to RM (SAF2008-02042) and JM (SAF2006-12520-C02-02 and BFU2009-07206), from the Fundación Marqués de Valdecilla, Spain to JM (API-07/02), by a research agreement sponsored by Novartis Vaccines and Diagnostics (to R. M. and J. M.), by grant REDINREN RD06/0016 from the ‘‘Instituto de Salud Carlos III’’ to R. M. and by grant no LSHP-CT- 2003–503240 (MUVAPRED, Mucosal Vaccines for Poverty Related Diseases) from the ‘‘European Commission’’ to G. D. G. and R. R. |
| Databáze: | OpenAIRE |
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