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The IL-6-deficient mouse exhibits impaired lymphocytic responses to a vaccine combining live Leishmania major and CpG oligodeoxynucleotides

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Abstract:

We have previously reported that vaccination with CpG oligodeoxynucleotides delivered concomitantly with live Leishmania major (Lm/CpG) eliminates lesions associated with live vaccination in C57BL/6 mice. The absence of lesions is at least in part a result of the CpG DNA-mediated activation of dermal dendritic cells to produce cytokines such as interleukin (IL)-6. Wild-type C57BL/6 mice and IL-6−/− mice were immunized with the Lm/CpG vaccine and monitored for the development of lesions. IL-6−/− mice developed extensive, nonhealing lesions following live vaccination. The analysis of the inoculation site and draining lymph nodes of the IL-6−/− mice revealed a constitutive reduction in lymphocyte numbers, particularly CD4+ T cells. Live vaccination resulted in the specific expansion of CD4+Foxp3+ regulatory T cells in the knockout mice, and in a decrease of CD4+ IFN- -producing cells. These results indicate that IL-6−/− mice may have collateral immune defects that could influence the development of the natural immune response to pathogens, vaccines, or other inflammatory stimuli.

Nous avions précédemment rapporté que la vaccination avec des oligonucléotides CpG administrés de façon concomitante avec Leishmania major (Lm/CpG) vivant éliminait les lésions associées au vaccin vivant chez les souris C57BL/6. L’absence de lésions est le résultat, du moins en partie, de l’activation des cellules dendritiques dermiques par l’ADN CpG à produire des cytokines dont l’interleukine-6 (IL-6). Des souris C57BL/6 sauvages et IL-6−/− ont été immunisées avec le vaccin Lm/CpG et examinées relativement au développement de lésions. Les souris IL-6−/− développaient des lésions envahissantes et non-guérissables après l’administration du vaccin vivant. L’analyse du site d’inoculation et des ganglions lymphatiques drainants des souris IL-6−/− a révélé une réduction constitutive du nombre de lymphocytes, notamment des cellules T CD4+. Le vaccin vivant causait une expansion des cellules T régulatrices CD4+ Foxp3+ chez les souris déficientes, et une diminution des cellules CD4+ productrices d’IFN-. Ces résultats indiquent que les souris IL-6−/− peuvent avoir des déficiences immunitaires collatérales qui pourraient influencer le développement d’une réponse immune naturelle envers les pathogènes, les vaccins ou d’autres stimulus inflammatoires.

Document Type: Research Article

Publication date: June 1, 2009

More about this publication?
  • Published since 1954, this monthly journal contains new research in the field of microbiology including applied microbiology and biotechnology; microbial structure and function; fungi and other eucaryotic protists; infection and immunity; microbial ecology; physiology, metabolism and enzymology; and virology, genetics, and molecular biology. It also publishes review articles and notes on an occasional basis, contributed by recognized scientists worldwide.
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