{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T04:16:54Z","timestamp":1789186614168,"version":"build-2803163510"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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\u2013Gu\u00e9rin (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\u2013derived dendritic cells and the activation of T cells compared with those with rBCG-pSO. The amounts of IFN-\u03b3, TNF-\u03b1, and IL-6 produced by splenocytes of rBCG-SOCS1DN\u2013immunized mice were larger than those produced by splenocytes of rBCG-pSO\u2013immunized mice. Moreover, the rBCG-SOCS1DN\u2013immunized 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.<\/jats:p>","DOI":"10.4049\/jimmunol.1800694","type":"journal-article","created":{"date-parts":[[2019,5,17]],"date-time":"2019-05-17T20:06:30Z","timestamp":1558123590000},"page":"188-197","source":"Crossref","is-referenced-by-count":10,"title":["SOCS1 Antagonist\u2013Expressing Recombinant Bacillus Calmette\u2013Gu\u00e9rin Enhances Antituberculosis Protection in a Mouse Model"],"prefix":"10.1093","volume":"203","author":[{"given":"Satoru","family":"Mizuno","sequence":"first","affiliation":[{"name":"Department of Molecular and Experimental Medicine, Mie University Graduate School of Medicine , Tsu, Mie 514-8507 ,","place":["Japan"]},{"name":"Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition , Tsukuba, Ibaraki 305-0843 ,","place":["Japan"]},{"name":"Research and Development Department, Japan BCG Laboratory , Kiyose, Tokyo 204-0022 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7990-8403","authenticated-orcid":false,"given":"Shogo","family":"Soma","sequence":"additional","affiliation":[{"name":"Department of Molecular and Experimental Medicine, Mie University Graduate School of Medicine , Tsu, Mie 514-8507 ,","place":["Japan"]},{"name":"Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition , Tsukuba, Ibaraki 305-0843 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyasu","family":"Inada","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Suzuka University of Medical Science , Suzuka, Mie 513-8670 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1020-398X","authenticated-orcid":false,"given":"Tomohiro","family":"Kanuma","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition , Tsukuba, Ibaraki 305-0843 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition , Tsukuba, Ibaraki 305-0843 ,","place":["Japan"]},{"name":"Research and Development Department, Japan BCG Laboratory , Kiyose, Tokyo 204-0022 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8252-1448","authenticated-orcid":false,"given":"Yasuhiro","family":"Yasutomi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Experimental Medicine, Mie University Graduate School of Medicine , Tsu, Mie 514-8507 ,","place":["Japan"]},{"name":"Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition , Tsukuba, Ibaraki 305-0843 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,1]]},"reference":[{"key":"2025030418133039900_r1","author":"World Health Organization","year":"2017"},{"key":"2025030418133039900_r2","author":"World Health Organization","year":"2007"},{"key":"2025030418133039900_r3","doi-asserted-by":"crossref","first-page":"12434","DOI":"10.1073\/pnas.0703510104","article-title":"Poor correlation between BCG vaccination-induced T cell responses and protection against tuberculosis","volume":"104","author":"Mittr\u00fccker","year":"2007","journal-title":"Proc. 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