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

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机构： [1]Department of Dermatology and Venereology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China [2]College of Pharmaceutical Sciences, Yunnan University of Traditional Chinese Medicine, Kunming, 650500, China [3]Scientific Research Laboratory Center, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China [4]Hubei Provincial Key Laboratory of Occurrence and Intervention of Kidney Diseases, Medical College, Hubei Polytechnic University, Huangshi, China

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关键词： Talaromyces marneffei Macrophages Pyroptosis Thalidomide NLRP3 Caspase-1 Mice model HIV

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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 macrophages, 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 deteriorated. 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.Copyright © 2023. Published by Elsevier Ltd.

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大类 | 3 区医学

小类 | 3 区免疫学 3 区微生物学

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出版当年[2023]版：

Q2 MICROBIOLOGY Q3 IMMUNOLOGY

最新[2023]版：

Q2 MICROBIOLOGY Q3 IMMUNOLOGY

影响因子： 3.3 最新[2023版] 3.6 最新五年平均 3.3 出版当年[2023版] 3.6 出版当年五年平均 3.8 出版前一年[2022版]

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第一作者机构： [1]Department of Dermatology and Venereology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China [4]Hubei Provincial Key Laboratory of Occurrence and Intervention of Kidney Diseases, Medical College, Hubei Polytechnic University, Huangshi, China

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