Increased pulmonary tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-17A responses compensate for decreased gamma interferon production in anti-IL-12 autovaccine-treated, Mycobacterium bovis BCG-vaccinated mice
| Autor: | Danielle Freches, Jacques Van Snick, Kris Huygen, Hannelie Korf, Catherine Uyttenhove, Jean-Christophe Renauld, Marta Romano |
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| Přispěvatelé: | UCL - SSS/DDUV - Institut de Duve |
| Rok vydání: | 2010 |
| Předmět: |
Microbiology (medical)
medicine.medical_treatment Interferon-gamma - biosynthesis Clinical Biochemistry Immunology Down-Regulation Lung - immunology metabolism Mycobacterium bovis - immunology BCG Vaccine - administration & dosage immunology Mycobacterium tuberculosis Tuberculosis - immunology prevention & control Interferon-gamma Mice medicine Autovaccines - administration & dosage immunology Immunology and Allergy Animals Tuberculosis Interferon gamma Lung Mycobacterium bovis biology Interleukin-6 Tumor Necrosis Factor-alpha Interleukin-17 biology.organism_classification Vaccine Research Interleukin-6 - metabolism Interleukin-12 Interleukin-12 - immunology Up-Regulation Mice Inbred C57BL Cytokine Tumor Necrosis Factor-alpha - metabolism Interleukin 12 Autovaccines BCG Vaccine Interleukin-17 - metabolism Female Immunization Interleukin 17 Tuberculosis vaccines BCG vaccine medicine.drug |
| Zdroj: | Clinical and Vaccine Immunology, Vol. 18, no. 1, p. 95-104 (2011) |
| ISSN: | 1556-679X |
| Popis: | Interleukin-12 (IL-12) and IL-23 (which share a p40 subunit) are pivotal cytokines in the generation of protective Th1/Th17-type immune responses upon infection with the intracellular pathogen Mycobacterium tuberculosis . The role of IL-12 and IL-23 in protection conferred by the tuberculosis vaccine Mycobacterium bovis bacillus Calmette-Guérin (BCG) is, however, less well documented. By using an autovaccine approach, i.e., IL-12p70 cross-linked with ovalbumin and PADRE peptide formulated with the GSK proprietary adjuvant system AS02 V , we could specifically neutralize IL-12 while leaving the IL-23 axis intact. Neutralization of IL-12 before M. tuberculosis challenge rendered C57BL/6 mice highly susceptible, resulting in 30-fold-higher CFU in spleen and lungs and accelerated mortality. In contrast, neutralization of IL-12 in BCG-vaccinated mice prior to M. tuberculosis challenge only marginally affected vaccine-mediated protection. Analysis of cytokine production in spleen and lungs 3 weeks post-TB challenge by enzyme-linked immunosorbent assay and functional and flow cytometric assays showed significantly reduced mycobacterium-specific gamma interferon (IFN-γ) responses in M. tuberculosis -infected and BCG-vaccinated mice that had been treated with the autovaccine. Purified protein derivative-induced tumor necrosis factor alpha (TNF-α), IL-6, and IL-17A levels, however, were highest in lungs from BCG-vaccinated/IL-12-neutralized animals, and even unstimulated lung cells from these mice produced significant levels of the three cytokines. Mycobacterium-specific IL-4 and IL-5 production levels were overall very low, but IL-12 neutralization resulted in increased concanavalin A-triggered polyclonal secretion of these Th2-type cytokines. These results suggest that TNF-α, IL-6, and IL-17A may be more important pulmonary effector molecules of BCG-mediated protection than IFN-γ in a context of IL-12 deficiency. |
| Databáze: | OpenAIRE |
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