{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T13:02:56Z","timestamp":1779714176760,"version":"3.53.1"},"reference-count":48,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Central Guidance on Local Science and Technology Development Fund of Shanxi Province","award":["YDZJSX20231A005"],"award-info":[{"award-number":["YDZJSX20231A005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Butyrophilin-like 2 (BTNL2) is an immunomodulatory molecule critically involved in regulating the host immune response to infection with the avirulent Mycobacterium tuberculosis strain H37Ra. However, its functional role in modulating pyroptosis and associated inflammatory responses remains incompletely characterized. Here, we demonstrate that BTNL2 deficiency exacerbates pyroptosis and the inflammatory response in H37Ra-infected murine peritoneal macrophages via two distinct pathways. First, the loss of BTNL2 induces excessive mitochondrial damage, which leads to aberrant release of mitochondrial DNA (mtDNA) and accumulation of mitochondrial reactive oxygen species (mtROS), thereby triggering NLRP3 (NOD-like receptor family pyrin domain containing 3) inflammasome activation and gasdermin D (GSDMD)-mediated pyroptosis. Second, cytosolic mtDNA accumulation hyperactivates the cGAS\u2013STING signaling axis, resulting in transcriptional upregulation of NLRP3 and consequent amplification of pro-inflammatory cytokine production. Collectively, these findings demonstrate that BTNL2 acts as a regulator of mitochondrial homeostasis and innate immune balance during H37Ra infection in primary peritoneal macrophages. The results provide mechanistic insights into BTNL2 function in the context of H37Ra-induced pyroptosis.<\/jats:p>","DOI":"10.3390\/microorganisms14061188","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T11:57:44Z","timestamp":1779710264000},"page":"1188","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["BTNL2 Inhibits Pyroptosis in H37Ra-Infected Macrophages by Maintaining Mitochondrial Homeostasis"],"prefix":"10.3390","volume":"14","author":[{"given":"Yazhi","family":"Feng","sequence":"first","affiliation":[{"name":"Key Laboratory of Medical Molecular and Cellular Biology of Shanxi Province, Institutes of Biomedical Sciences, Shanxi University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyao","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular and Cellular Biology of Shanxi Province, Institutes of Biomedical Sciences, Shanxi University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangxin","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular and Cellular Biology of Shanxi Province, Institutes of Biomedical Sciences, Shanxi University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7416-1662","authenticated-orcid":false,"given":"Changxin","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular and Cellular Biology of Shanxi Province, Institutes of Biomedical Sciences, Shanxi University, Taiyuan 030006, China"},{"name":"Biomedicine and Health Laboratory in Shanxi Province, Shanxi University, Taiyuan 030006, China"},{"name":"Key Laboratory of Chemical Biology and Molecular Engineering of Education Ministry, Shanxi University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102502","DOI":"10.1016\/j.tube.2024.102502","article-title":"METTL3-deficiency m6A-dependently degrades MALAT1 to suppress NLRP3-mediated pyroptotic cell death and inflammation in Mycobacterium tuberculosis (H37Ra strain)-infected mouse macrophages","volume":"146","author":"Han","year":"2024","journal-title":"Tuberculosis"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ye, Y., Liu, J., Guo, Y., Gao, Y., Rao, J., Su, R., Zhang, L., Huang, Z., Luo, Q., and Li, J. 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