title: The Transcriptional Foundations of Sp110-mediated Macrophage (RAW264.7) Resistance to Mycobacterium tuberculosis H37Ra.
abstract: Human tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a leading global health problem, causing 1.3 million deaths each year. The nuclear body protein, Sp110, has been linked to TB resistance and previous work showed that it enhances macrophage apoptosis upon Mtb infection. Here, we report on the role of Sp110 in transcriptional regulation of macrophage responses to Mtb through integrated transcriptome and mechanistic studies. Transcriptome analysis revealed that Sp110 regulates genes involved in immune responses, apoptosis, defence responses, and inflammatory responses. Detailed investigation revealed that, in addition to apoptosis-related genes, Sp110 regulates cytokines, chemokines and genes that regulate intracellular survival of Mtb. Moreover, Sp110 regulates miRNA expression in macrophages, with immune and apoptosis-related miRNAs such as miR-125a, miR-146a, miR-155, miR-21a and miR-99b under Sp110 regulation. Additionally, our results showed that Sp110 upregulates BCL2 modifying factor (Bmf) by inhibiting miR-125a, and forced expression of Bmf induces macrophage apoptosis. These findings not only reveal the transcriptional basis of Sp110-mediated macrophage resistance to Mtb, but also suggest potential regulatory roles for Sp110 related to inflammatory responses, miRNA profiles, and the intracellular growth of Mtb.
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China.|Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Yongyan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China.|Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Zekun
authors.initials: Z
authors.lastname: Guo
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China.|Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Kezhen
authors.initials: K
authors.lastname: Yao
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China.|Innovative Experimental College, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Miao
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China.|Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Shuxin
authors.initials: S
authors.lastname: Liang
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China.|Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Fayang
authors.initials: F
authors.lastname: Liu
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China.|Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China.|Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D018925:Chemokines / Q000378:metabolism; D016000:Cluster Analysis; D016207:Cytokines / Q000378:metabolism; D060467:Disease Resistance / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000382:microbiology* / Q000502:physiology*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D050296:Microbial Viability / Q000276:immunology; D015778:Minor Histocompatibility Antigens / Q000235:genetics*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009687:Nuclear Proteins / Q000235:genetics*; D014158:Transcription, Genetic; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology / Q000382:microbiology
chemical_list: D018925:Chemokines; D016207:Cytokines; D035683:MicroRNAs; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; C000598498:Sp110 protein, mouse