{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T20:49:57Z","timestamp":1793306997613,"version":"4.5.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T00:00:00Z","timestamp":1728000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Tuberculosis(TB), an infectious disease caused by <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (Mtb) infections, remains the leading cause of mortality from a single infectious agent globally. The progression of tuberculosis disease is contingent upon the complex interplay between the host\u2019s immune system and the pathogen Mtb. Interleukin-26 (IL-26), the most recently identified cytokine belonging to the IL-10 family, exhibits both extracellular antimicrobial properties and pro-inflammatory functions. However, the precise role of IL-26 in the host immune defense against Mtb infections and intracellular killing remains largely unexplored. In this study, we observed significantly elevated IL-26 mRNA expression in peripheral blood mononuclear cells of active-TB patients compared to healthy individuals. Conversely, circulating IL-26 levels in the plasma of adult TB patients were markedly lower than those of healthy cohorts. We purified recombinant IL-26 from an <jats:italic>E<\/jats:italic>. coli expression system using the Ni-NTA resin. Upon stimulations with the recombinant IL-26, human THP1 cells exhibited rapid morphological changes characterized by increased irregular spindle shape and formation of granular structures. Treating THP1 cells with IL-26 can also lead to heightened expressions of <jats:italic>CD80<\/jats:italic>, <jats:italic>TNF-\u03b1<\/jats:italic>, and <jats:italic>iNOS<\/jats:italic> but not <jats:italic>CD206<\/jats:italic> and <jats:italic>Arg1<\/jats:italic> in these cells, indicating an M1 macrophage differentiation phenotype. Furthermore, our investigations revealed a dose-dependent escalation of reactive oxygen species production, decreased mitochondrial membrane potential, and enhanced autophagy flux activity in THP1 macrophages following IL-26 treatment. Moreover, our results demonstrated that IL-26 contributed to the elimination of intracellular Mycobacterium tuberculosis via orchestrated ROS production. In conclusion, our findings elucidated the role of IL-26 in the development of tuberculosis and its contributions to intracellular bacilli killing by macrophages through the induction of M1-polarization and ROS production. These insights may have significant implications for understanding the pathogenesis of tuberculosis and developing novel therapeutic strategies.<\/jats:p>","DOI":"10.3389\/fcimb.2024.1455819","type":"journal-article","created":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T05:11:06Z","timestamp":1728018666000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Interleukin-26 expression in tuberculosis disease and its regulatory effect in macrophage polarization and intracellular elimination of Mycobacterium tuberculosis"],"prefix":"10.3389","volume":"14","author":[{"given":"Kaisong","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyun","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfang","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luxin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Ouyang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangxian","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2021.02.107","article-title":"Global Tuberculosis Report 2020 - Reflections on the Global TB burden, treatment and prevention efforts","volume":"113","author":"Chakaya","year":"2021","journal-title":"Int. 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