2. Academic Validation
  3. Induction of ASC pyroptosis requires gasdermin D or caspase-1/11-dependent mediators and IFNβ from pyroptotic macrophages

Induction of ASC pyroptosis requires gasdermin D or caspase-1/11-dependent mediators and IFNβ from pyroptotic macrophages

  • Cell Death Dis. 2020 Jun 18;11(6):470. doi: 10.1038/s41419-020-2664-0.
Cuiping Zhang 1 2,  Caiqi Zhao 3 4,  Xiaoyan Chen 1,  Rujia Tao 5,  Sijiao Wang 1 2,  Guangxun Meng 6,  Xing Liu 7,  Changzhou Shao 8 9,  Xiao Su 10 11
Affiliations

Affiliations

  • 1 Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, 200032, Shanghai, China.
  • 2 Department of Pulmonary Medicine, Xiamen Branch, Zhongshan Hospital, Fudan University, 361015, Xiamen, China.
  • 3 Unit of Respiratory Infection and Immunity, Institut Pasteur of Shanghai, Chinese Academy of Sciences, 200031, Shanghai, China.
  • 4 University of Chinese Academy of Sciences, 100039, Beijing, China.
  • 5 Department of Pulmonary and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University, 200433, Shanghai, China.
  • 6 The Center for Microbes, Development and Health, Unit of Innate Immunity, Institut Pasteur of Shanghai, Chinese Academy of Sciences, 200031, Shanghai, China.
  • 7 The Center for Microbes, Development and Health, Unit of Anti-Infective Immunity and Immune Diseases, Institut Pasteur of Shanghai, Chinese Academy of Sciences, 200031, Shanghai, China.
  • 8 Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, 200032, Shanghai, China. [email protected].
  • 9 Department of Pulmonary Medicine, Xiamen Branch, Zhongshan Hospital, Fudan University, 361015, Xiamen, China. [email protected].
  • 10 Unit of Respiratory Infection and Immunity, Institut Pasteur of Shanghai, Chinese Academy of Sciences, 200031, Shanghai, China. [email protected].
  • 11 University of Chinese Academy of Sciences, 100039, Beijing, China. [email protected].
PMID: 32555186 DOI: 10.1038/s41419-020-2664-0
Abstract

Mesenchymal stem cells (MSCs) have been used in cell-based therapies for a variety of disorders. Some factors such as inflammatory mediators in the diseased area might damage the survival of MSCs and affect their efficacy. Pyroptosis is a form of programmed necrosis as a response for immune cells to cytosolic pathogenic stimuli. Whether MSCs develop Pyroptosis under pathological stimulation, its underlying mechanism and biological significance are still unclear. Here, we found that LPS, flagellin, dsDNA, nigericin (NIG), or LPS combined with nigericin (LPS/NIG) could not induce Pyroptosis in adipose-tissue-derived mesenchymal stem cells (ASCs). However, when applied the culture media collected from LPS/NIG-induced pyroptotic bone marrow-derived macrophages (BMDMs) to incubate ASCs, ASCs developed Pyroptosis. Inhibition of caspases or deletion of Caspase-1/11 in ASCs did not affect the pyroptotic macrophage media-triggered ASC Pyroptosis while ablation of Caspase-1/11 abolished BMDM Pyroptosis induced by LPS/NIG. Media collected from LPS/NIG stimulated Gsdmd-/- or Caspase-1/11-/- BMDMs could not induce Pyroptosis of ASCs. In addition, RNA-seq analysis showed that interferon (IFN)-stimulated genes were upregulated in pyroptotic ASCs. Adding IFNβ could boost LPS/NIG stimulated BMDM media-induced ASC Pyroptosis. Surprisingly, the pyroptotic ASCs had a lower bactericidal ability to P. Aeruginosa. Taken together, induction of ASC Pyroptosis requires gasdermin D or Caspase-1/11-dependent mediators and IFNβ from pyroptotic macrophages.

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