Microbes and infection · 2025
LncSSBP1/FOXO3 axis modulates autophagy: a novel insight into bronchial epithelial cells defense against Talaromyces marneffei infection.
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Lin Lu, Pan Shitong, Xu Mingpeng, Chen Huan, He Zhiyi, Li Yinghua
Аннотация
BACKGROUND: While autophagy is pivotal in antimicrobial defense, its regulatory role in Talaromyces marneffei (TM) infected bronchial epithelium remains elusive.
OBJECTIVE: To elucidate the impact of TM infection on autophagy in bronchial epithelial cells and to identify the key molecular regulators involved in this process.
METHODS: Primary computational screening identified core autophagy modulators. Autophagy flux was monitored through LC3B-II/P62 immunoblotting and transmission electron microscopy. Mechanistic validation was performed using siRNA-mediated FOXO3 silencing, lentivirus-mediated lncSSBP1 knockdown and overexpression cell models, combined with immunofluorescence staining for nuclear localization.
RESULTS: Bioinformatics analysis identified seven autophagy modulating effectors, with FOXO3 emerging as the central regulator. Quantitative proteomics revealed biphasic autophagic responses: initial LC3B-II accumulation with P62 degradation at 4h post-infection, followed by P62 rebound at 24h, indicating time-dependent flux impairment. FOXO3 was identified as a critical mediator of TM-induced autophagy. Furthermore, we identified a strong positive correlation between lncSSBP1 and FOXO3 expression, with lncSSBP1 overexpression enhancing FOXO3 levels and promoting autophagosome maturation.
CONCLUSION: This study uncovers a previously unrecognized lncRNA-mediated regulatory axis wherein lncSSBP1 orchestrates FOXO3-driven autophagy during TM infection. These results provide new insights into the molecular mechanisms of host-pathogen interactions.
OBJECTIVE: To elucidate the impact of TM infection on autophagy in bronchial epithelial cells and to identify the key molecular regulators involved in this process.
METHODS: Primary computational screening identified core autophagy modulators. Autophagy flux was monitored through LC3B-II/P62 immunoblotting and transmission electron microscopy. Mechanistic validation was performed using siRNA-mediated FOXO3 silencing, lentivirus-mediated lncSSBP1 knockdown and overexpression cell models, combined with immunofluorescence staining for nuclear localization.
RESULTS: Bioinformatics analysis identified seven autophagy modulating effectors, with FOXO3 emerging as the central regulator. Quantitative proteomics revealed biphasic autophagic responses: initial LC3B-II accumulation with P62 degradation at 4h post-infection, followed by P62 rebound at 24h, indicating time-dependent flux impairment. FOXO3 was identified as a critical mediator of TM-induced autophagy. Furthermore, we identified a strong positive correlation between lncSSBP1 and FOXO3 expression, with lncSSBP1 overexpression enhancing FOXO3 levels and promoting autophagosome maturation.
CONCLUSION: This study uncovers a previously unrecognized lncRNA-mediated regulatory axis wherein lncSSBP1 orchestrates FOXO3-driven autophagy during TM infection. These results provide new insights into the molecular mechanisms of host-pathogen interactions.