SOCS1 Antagonist–Expressing Recombinant Bacillus Calmette–Guérin Enhances Antituberculosis Protection in a Mouse Model
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Le résumé fourni par la source
Abstract Suppressor of cytokine signaling 1 (SOCS1) plays a key role in the negative regulation of JAK/STAT signaling, which is involved in innate immunity and subsequent adaptive immunity. Bacillus Calmette–Guérin (BCG) induces upregulation of SOCS1 expression in host cells, which may lead to the suppression of immune responses by BCG via inhibition of the JAK/STAT signaling pathway. This might cause A reduction in the protective effect of a BCG vaccine. In the current study, we assessed the immune responses to and the protective efficacy of a recombinant BCG secreting a dominant negative mutant of the SOCS1 molecule (rBCG-SOCS1DN). C57BL/6 mice were immunized with rBCG-SOCS1DN or parental BCG Tokyo vaccine strain harboring an empty plasmid vector (rBCG-pSO). rBCG-SOCS1DN enhanced the activation of bone marrow–derived dendritic cells and the activation of T cells compared with those with rBCG-pSO. The amounts of IFN-γ, TNF-α, and IL-6 produced by splenocytes of rBCG-SOCS1DN–immunized mice were larger than those produced by splenocytes of rBCG-pSO–immunized mice. Moreover, the rBCG-SOCS1DN–immunized mice showed a substantial reduction in the number of CFU of Mycobacterium tuberculosis in the lungs and spleens compared with that in control BCG-immunized mice when the immunized mice were infected with a highly pathogenic M. tuberculosis strain by inhalation. These findings provide evidence for the possibility of rBCG-SOCS1DN being an effective M. tuberculosis vaccine with a novel concept of rBCG as a tool for immunomodulation in host cells.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- SOCS1 Antagonist–Expressing Recombinant Bacillus Calmette–Guérin Enhances Antituberculosis Protection in a Mouse Model
- Date Crossref
- 01/07/2019
- Éditeur
- Oxford University Press (OUP)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Mie University Department of Molecular and Experimental Medicine pays non établi dans la noticeUniversité ou école supérieure
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National Institute of Biomedical Innovation pays non établi dans la noticeStructure de recherche
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Japan BCG Laboratory Research and Development Department pays non établi dans la noticeStructure de recherche
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Suzuka University of Medical Science Department of Pharmaceutical Sciences pays non établi dans la noticeUniversité ou école supérieure
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Laboratory of Immunoregulation and Vaccine Research pays non établi dans la noticeStructure de recherche
Department of Molecular and Experimental Medicine — Mie University, National Institute of Biomedical Innovation et Research and Development Department — Japan BCG Laboratory, avec 2 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.