Table_1_Transcription factor MAFB controls type I and II interferon response-mediated host immunity in Mycobacterium tuberculosis-infected macrophages.PDF

MAFB, v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B, has been identified as a candidate gene for early tuberculosis (TB) onset in Thai and Japanese populations. Here, we investigated the genome-wide transcriptional profiles of MAFB-knockdown (KD) macrophages infected with Mycobacterium tuberculosis (Mtb) to highlight the potential role of MAFB in host immunity against TB. Gene expression analysis revealed impaired type I and type II interferon (IFN) responses and enhanced oxidative phosphorylation in MAFB-KD macrophages infected with Mtb. The expression of inflammatory chemokines, including IFN-γ-inducible genes, was confirmed to be significantly reduced by knockdown of MAFB during Mtb infection. A similar effect of MAFB knockdown on type I and type II IFN responses and oxidative phosphorylation was also observed when Mtb-infected macrophages were activated by IFN-γ. Taken together, our results demonstrate that MAFB is involved in the immune response and metabolism in Mtb-infected macrophages, providing new insight into MAFB as a candidate gene to guide further study to control TB.

MAFB（v-maf禽肌肉腱膜纤维肉瘤癌基因同源物B）已被鉴定为泰国与日本人群结核病（tuberculosis, TB）早发的候选易感基因。本研究针对结核分枝杆菌（Mycobacterium tuberculosis, Mtb）感染的MAFB基因敲低（KD）巨噬细胞开展全基因组转录组谱分析，以阐明MAFB在宿主抗结核病免疫中的潜在功能。基因表达分析结果显示，在Mtb感染的MAFB敲低巨噬细胞中，I型与II型干扰素（IFN）应答受损，而氧化磷酸化水平上调。研究证实，结核分枝杆菌感染期间，MAFB敲低可显著下调包括干扰素-γ（IFN-γ）诱导基因在内的炎性趋化因子的表达。当经IFN-γ激活Mtb感染的巨噬细胞时，同样观察到MAFB敲低对I、II型干扰素应答及氧化磷酸化的相似调控效应。综上，本研究结果表明MAFB参与结核分枝杆菌感染巨噬细胞的免疫应答与代谢调控过程，为将MAFB作为候选基因指导结核病防控的后续研究提供了全新视角。