{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T22:35:08Z","timestamp":1783377308556,"version":"3.54.6"},"reference-count":31,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,24]],"date-time":"2024-11-24T00:00:00Z","timestamp":1732406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32072942"],"award-info":[{"award-number":["32072942"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2024AFB191"],"award-info":[{"award-number":["2024AFB191"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["CARS-37"],"award-info":[{"award-number":["CARS-37"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Youth Program of Natural Science Foundation of Hubei Province","award":["32072942"],"award-info":[{"award-number":["32072942"]}]},{"name":"Youth Program of Natural Science Foundation of Hubei Province","award":["2024AFB191"],"award-info":[{"award-number":["2024AFB191"]}]},{"name":"Youth Program of Natural Science Foundation of Hubei Province","award":["CARS-37"],"award-info":[{"award-number":["CARS-37"]}]},{"name":"China Agriculture Research System of MOF and MARA","award":["32072942"],"award-info":[{"award-number":["32072942"]}]},{"name":"China Agriculture Research System of MOF and MARA","award":["2024AFB191"],"award-info":[{"award-number":["2024AFB191"]}]},{"name":"China Agriculture Research System of MOF and MARA","award":["CARS-37"],"award-info":[{"award-number":["CARS-37"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Tuberculosis (TB), primarily caused by Mycobacterium tuberculosis (M. tb) and Mycobacterium\u00a0bovis (M. bovis), remains the leading cause of death from a single infectious agent globally. Intracellular survival is crucial for their virulence; yet, the underlying mechanisms are not fully understood. This study aimed to demonstrate the significance of a previously unannotated bovine gene ENSBTAG00000011305 in M. bovis intracellular survival. This gene was termed NMRAL2_Bovine due to its inclusion of the NmrA domain which has a relation to nitric oxide (NO) production. We used CRISPR\/Cas9 to knock out NMRAL2_Bovine in bovine lung epithelial cells and observed a significant decrease in M. bovis-induced cell death and the intracellular bacterial count, alongside increased NO levels. A transcriptome analysis revealed the upregulation of pathways linked to NO, IL-6, and TNF-\u03b1 production, which was confirmed by the increased expression of iNOS, IL-6, and TNF-\u03b1. Correspondingly, Western blotting indicated that key signaling pathways, including NF-\u03baB and MAPK, were activated. In conclusion, our findings determined that NMRAL2_Bovine functions as a negative regulator of the inflammatory response induced by M. bovis infection at the cellular level and, thereby, provide a novel insight into TB pathogenesis and a potential target for developing novel host-directed therapies against TB.<\/jats:p>","DOI":"10.3390\/cells13231953","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T05:21:32Z","timestamp":1732512092000},"page":"1953","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Bovine NMRAL2 Protein Blunts Nitric Oxide Production and Inflammatory Response in Mycobacterium bovis Infected Bovine Lung Epithelial Cells"],"prefix":"10.3390","volume":"13","author":[{"given":"Yongchong","family":"Peng","sequence":"first","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural 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