Transcriptional regulators <i>SP110</i> and <i>SP140</i> modulate inflammatory response genes in <i>Mycobacterium tuberculosis</i> -infected human macrophages

Tuberculosis (TB) is one of the most serious infectious diseases, with high morbidity and mortality worldwide. C3HeB/FeJ mice are widely utilized for evaluating anti-TB drugs because their drug sensitivity and pathology during <i>M. tuberculosis</i> infection resemble those of human TB, including the development of necrotizing granulomas. Downregulation of the transcriptional regulatory genes <i>Sp110</i> and <i>Sp140</i> in C3HeB/FeJ mice has been demonstrated to activate gene expression associated with inflammatory responses during <i>M. tuberculosis</i> infection, resulting in susceptibility to the infection. Here, we examined the regulatory manner of <i>SP110</i> and <i>SP140</i> using transcriptomic analysis in <i>M. tuberculosis</i>-infected human macrophages. Depletion of <i>SP110</i> and/or <i>SP140</i> in <i>M. tuberculosis</i>-infected THP-1 macrophages impaired the induction of gene expression associated with inflammatory responses, including interferon response genes, compared with that in control macrophages. These results suggest that human <i>SP110</i> and <i>SP140</i> act as positive regulators for genes associated with inflammatory responses upon <i>M. tuberculosis</i> infection.