Thalidomide promotes NLRP3/caspase-1-mediated pyroptosis of macrophages in Talaromyces marneffei infection

作者：Dong, Rong-Jin; Li, Jun; Zhang, Yi; Li, Jia-Sheng; Yang, Lu-Hui; Kuang, Yi-Qun^*; Wang, Rui-Rui^*; Li, Yu-Ye^*

来源：Microbial Pathogenesis, 2023, 181: 106168.

DOI：10.1016/j.micpath.2023.106168

• Talaromyces marneffei
• Macrophages
• Pyroptosis
• Thalidomide
• NLRP3
• Caspase-1
• Mice model
• HIV

Macrophage-derived inflammatory cytokines are critical for host defense against Talaromyces marneffei (T. marneffei) infection among HIV/AIDS patients, and excessive inflammatory cytokines are associated with poor outcomes of AIDS-associated talaromycosis. However, the underlying mechanisms of macrophage-caused pyroptosis and cytokine storm are poorly understood. Here, in the T. marneffei-infected mice and macro-phages, we show that T. marneffei induced pyroptosis in macrophages through the NLRP3/caspase-1 pathway. The immunomodulatory drug thalidomide could promote the pyroptosis of macrophages infected T. marneffei. In T. marneffei-infected mice, the splenic macrophages underwent increasing pyroptosis as talaromycosis deterio-rated. Thalidomide ameliorated inflammation of mice, while amphotericin B (AmB) in combination with thalidomide did not improve overall survival compared with AmB alone. Taken together, our findings suggest that thalidomide promotes NLRP3/caspase-1-mediated pyroptosis of macrophages in T. marneffei infection.

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