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Most of the brucellosis vaccines in the application are whole-bacteria vaccines. Live-attenuated vaccines are widely used for brucellosis prevention in sheep, goats, pigs, and cattle. Thus, there is also a need for an adjuvanted vaccine for human brucellosis, because the attenuated Brucella vaccines now utilized in animals cause human illness. Here, we developed a live-attenuated Brucella suis strain 2 vaccine (S2) adjuvanted with Ag85a (Ag85a-S2). We found that Ag85a-S2 activated cGAS-STING pathways both in intestinal mucosal cells in vivo and in the BMDM and U937 cell line in vitro. We demonstrated that the cGAS knockout significantly downregulated the abundance of interferon and other cytokines induced by Ag85a-S2. Moreover, Ag85a-S2 triggered a stronger cellular immune response compared to S2 alone. In sum, Ag85a-S2-mediated enhancement of immune responses was at least partially dependent on the cGAS-STING pathway. Our results provide a new candidate for preventing Brucella pathogens from livestock, which might reduce the dosage and potential toxicity compared to S2.<\/jats:p>","DOI":"10.3390\/vaccines10122170","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T06:24:44Z","timestamp":1671431084000},"page":"2170","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Ag85a-S2 Activates cGAS-STING Signaling Pathway in Intestinal Mucosal Cells"],"prefix":"10.3390","volume":"10","author":[{"given":"Sheng","family":"Dang","sequence":"first","affiliation":[{"name":"Innovative Institute of Zoonoses, Inner Mongolia Minzu University, Tongliao 028000, China"},{"name":"Keerqin District First People\u2019s Hospital, Tongliao 028000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanyang","family":"Li","sequence":"additional","affiliation":[{"name":"Innovative Institute of Zoonoses, Inner Mongolia Minzu University, Tongliao 028000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubo","family":"Wen","sequence":"additional","affiliation":[{"name":"Innovative Institute of Zoonoses, Inner Mongolia Minzu University, Tongliao 028000, China"},{"name":"Brucellosis Prevention and Treatment Engineering Research Center of Inner Mongolia Autonomous Region, Tongliao 028000, China"},{"name":"Key Laboratory of Zoonose Prevention and Control at Universities of Inner Mongolia Autonomous Region, Tongliao 028000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Song","sequence":"additional","affiliation":[{"name":"Innovative Institute of Zoonoses, Inner Mongolia Minzu University, Tongliao 028000, China"},{"name":"Brucellosis Prevention and Treatment Engineering Research Center of Inner Mongolia Autonomous Region, Tongliao 028000, China"},{"name":"Key Laboratory of Zoonose Prevention and Control at Universities of Inner Mongolia Autonomous Region, Tongliao 028000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meirong","family":"Bai","sequence":"additional","affiliation":[{"name":"Innovative Institute of Zoonoses, Inner Mongolia Minzu University, Tongliao 028000, China"},{"name":"Key Laboratory of Mongolian Medicine Research and Development Engineering, Ministry of Education, Tongliao 028000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyan","family":"Li","sequence":"additional","affiliation":[{"name":"Innovative Institute of Zoonoses, Inner Mongolia Minzu University, Tongliao 028000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeliang","family":"Chen","sequence":"additional","affiliation":[{"name":"Innovative Institute of Zoonoses, Inner Mongolia Minzu University, Tongliao 028000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8891-279X","authenticated-orcid":false,"given":"Jingbo","family":"Zhai","sequence":"additional","affiliation":[{"name":"Innovative Institute of Zoonoses, Inner Mongolia Minzu University, Tongliao 028000, China"},{"name":"Brucellosis Prevention and Treatment Engineering Research Center of Inner Mongolia Autonomous Region, Tongliao 028000, China"},{"name":"Key Laboratory of Zoonose Prevention and Control at Universities of Inner Mongolia Autonomous Region, Tongliao 028000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1016\/j.ajpath.2015.03.003","article-title":"Pathogenesis and Immunobiology of Brucellosis Review of Brucella-Host Interactions","volume":"185","author":"Figueiredo","year":"2015","journal-title":"Am. 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