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resurgence of brucellosis epidemics in China in recent years, the chances of a brucella coinfection with other common respiratory pathogens, such as the influenza virus, have increased dramatically. However, little is known about the pathogenicity or the mechanisms of brucella and influenza coinfections. (2) Methods: To clarify the interventions in the early stages of lung damage due to brucella and influenza coinfections, we evaluated the effect of the coinfection on disease progression and mortality using a coinfection model in WT mice and NLRP6\u2212\/\u2212 mice, and we verified the function of NLRP6 in infection and proinflammation. (3) Results: The coinfection induced significant respiratory symptoms, weight loss, and a high mortality rate in WT mice. Influenza in the coinfection group significantly increased brucella proliferation in a synergistic manner. Meanwhile, a histological examination showed severe lung tissue destruction and excessive inflammatory responses in coinfected WT animals, and the expression of NLRP6 and IL-18 was dramatically increased in the lung tissues. Furthermore, NLRP6 deletion attenuated lung injuries and inflammation, a reduced bacterial load, and decreased IL-18 protein expression. (4) Conclusions: Our findings indicated that NLRP6 plays a critical role and might be a promising potential therapeutic target for brucella\u2013influenza coinfections.<\/jats:p>","DOI":"10.3390\/jpm12122063","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T04:15:00Z","timestamp":1670991300000},"page":"2063","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["NLRP6 Induces Lung Injury and Inflammation Early in Brucella and Influenza Coinfection"],"prefix":"10.3390","volume":"12","author":[{"given":"Bochang","family":"Shi","sequence":"first","affiliation":[{"name":"Inner Mongolia Key Laboratory of Molecular Biology, Inner Mongolia Medical University, Hohhot 010000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Han","sequence":"additional","affiliation":[{"name":"Inner Mongolia Key Laboratory of Molecular Biology, Inner Mongolia Medical University, Hohhot 010000, China"},{"name":"Qingdao Binhai University, Qingdao 266000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huabin","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030600, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingyun","family":"Tan","sequence":"additional","affiliation":[{"name":"School of Basic Medicine Sciences, Anhui Medical University, Hefei 230000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyu","family":"Li","sequence":"additional","affiliation":[{"name":"School of Basic Medicine Sciences, Anhui Medical University, Hefei 230000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1973-9927","authenticated-orcid":false,"given":"Keyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing 100000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Li","sequence":"additional","affiliation":[{"name":"The Fifth Medical Center of PLA General Hospital, Beijing 100000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"He","sequence":"additional","affiliation":[{"name":"School of Basic Medicine Sciences, Anhui Medical University, Hefei 230000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chongyu","family":"Tian","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030600, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Yan","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030600, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanchun","family":"Shi","sequence":"additional","affiliation":[{"name":"Inner Mongolia Key Laboratory of Molecular Biology, Inner Mongolia Medical University, Hohhot 010000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanqiang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Inner Mongolia Key Laboratory of Molecular Biology, Inner Mongolia Medical University, Hohhot 010000, China"},{"name":"Beijing University of Chinese Medicine, Beijing 100000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongpeng","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Basic Medicine Sciences, Anhui Medical University, Hefei 230000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"237ra66","DOI":"10.1126\/scitranslmed.3008618","article-title":"The liver may act as a firewall mediating mutualism between the host and its gut commensal microbiota","volume":"6","author":"Balmer","year":"2014","journal-title":"Sci. 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