{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T18:50:10Z","timestamp":1764874210191,"version":"build-2065373602"},"reference-count":59,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T00:00:00Z","timestamp":1762646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Host innate immunity is crucial for orchestrating a protective response against dangerous pathogens. Herein, we demonstrate that interferon-inducible protein (IFI204), a DNA sensor, is implicated in protection against pulmonary pathogenic Mannheimia haemolytica (M. haemolytica) infection by driving inflammasome signaling activation. Ifi204\u2212\/\u2212 mice are more susceptible to pathogenic M. haemolytica infection compared with their wild-type (WT) counterparts, with decreased survival rates, extensive lung architecture destruction, exacerbated inflammatory cells infiltration, and more bacterial colonization. In vivo and in vitro findings elucidate that Ifi204 deficiency leads to a defect in inflammasome signaling activation, and exogenous recombinant IL-18 is sufficient to rescue the susceptibility of Ifi204\u2212\/\u2212 mice. Inflammasome signaling downstream of IFI204 facilitates early bacterial killing and clearance. Mechanistically, IFI204 promotes gasdermin D (GSDMD)-dependent inflammasome activation, and GSDMD is required for IFI204-mediated host defense. Notably, IFI204 detects pathogenic M. haemolytica-derived genomic DNA for the inflammasome signaling response. Thus, these data highlight the requirement of IFI204 in host defense response to M. haemolytica infection, and reveal that IFI204 may be a potential therapeutic target for pathogen control.<\/jats:p>","DOI":"10.3390\/microorganisms13112557","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T10:35:31Z","timestamp":1762770931000},"page":"2557","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["IFI204 Restricts Mannheimia haemolytica Pneumonia via Eliciting Gasdermin D-Dependent Inflammasome Signaling"],"prefix":"10.3390","volume":"13","author":[{"given":"Jia-Qi","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot 010070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot 010070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen-Yu","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot 010070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Jing","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot 010070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot 010070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot 010070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zi-Jian","family":"Zhuang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot 010070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ao-Bo","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot 010070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu-Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot 010070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot 010070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Sheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot 010070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1134-1715","authenticated-orcid":false,"given":"Shui-Xing","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot 010070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,9]]},"reference":[{"key":"ref_1","first-page":"D1128-50","article-title":"Molecular genetic analysis of virulence in Mannheimia (pasteurella) haemolytica","volume":"6","author":"Highlander","year":"2001","journal-title":"Front Biosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.mimet.2010.01.020","article-title":"Comparison of repetitive PCR and pulsed-field gel electrophoresis for the genotyping of Mannheimia haemolytica","volume":"81","author":"Klima","year":"2010","journal-title":"J. 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