2. Academic Validation
  3. Role of Histiocyte-Derived frHMGB1 as a Facilitator in Non-Canonical Pyroptosis of Monocytes/Macrophages in Lethal Sepsis

Role of Histiocyte-Derived frHMGB1 as a Facilitator in Non-Canonical Pyroptosis of Monocytes/Macrophages in Lethal Sepsis

  • J Infect Dis. 2024 Jan 19:jiae020. doi: 10.1093/infdis/jiae020.
Yu Tian 1 2,  Yuwen Cao 1 2,  Fang Liu 1 2,  Lin Xia 1 3,  Chao Wang 1 2,  Zhaoliang Su 1 2
Affiliations

Affiliations

  • 1 Institute for Medical Immunology, Affiliated Hospital of Jiangsu University, Zhenjiang, China, 212013.
  • 2 International Genome Center, Jiangsu University, Zhenjiang, China, 212013.
  • 3 Department of Laboratory Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, China, 212001.
PMID: 38243905 DOI: 10.1093/infdis/jiae020
Abstract

In this study, we investigated the role of the non-canonical Pyroptosis pathway in the progression of lethal sepsis. Our findings emphasize the significance of non-canonical Pyroptosis in monocytes/macrophages for the survival of septic mice. We observed that inhibiting Pyroptosis alone significantly improved the survival rate of septic mice, and the HMGB1 A box effectively suppressed this non-canonical Pyroptosis, thereby enhancing the survival of septic mice. Additionally, our cell in vitro experiments further unveil that frHMGB1, originating from LPS-carrying histiocytes, enters macrophages via RAGE, resulting in the direct activation of caspase-11 and the induction of non-canonical Pyroptosis. Notably, the A Box's competitive binding with LPS thereby impedes its entry into the cell cytosol. These findings reveal potential therapeutic strategies for slowing the progression of lethal sepsis by modulating the non-canonical Pyroptosis pathway.

Keywords

HMGB1; Macrophage; Pyroptosis; Sepsis.

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