Cell reports (Cambridge), 2021-04, Vol.35 (3), p.109012-109012, Article 109012
2021
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- Autor(en) / Beteiligte
- Titel
- Hierarchical cell-type-specific functions of caspase-11 in LPS shock and antibacterial host defense
- Ist Teil von
- Cell reports (Cambridge), 2021-04, Vol.35 (3), p.109012-109012, Article 109012
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2021
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Caspase-11 sensing of intracellular lipopolysaccharide (LPS) plays critical roles during infections and sepsis. However, the key cell types that sense intracellular LPS and their contributions to the host responses at the organismal level are not completely clear. Here, we show that macrophage/monocyte-specific caspase-11 plays a dominant role in mediating the pathological manifestations of endotoxemia, including gasdermin D (GSDMD) activation, interleukin (IL)-1β, IL-18, and damage-associated molecular pattern (DAMP) release, tissue damage, and death. Surprisingly, caspase-11 expression in CD11c+ cells and intestinal epithelial cells (IECs) plays minor detrimental roles in LPS shock. In contrast, caspase-11 expression in neutrophils is dispensable for LPS-induced lethality. Importantly, caspase-11 sensing of intracellular LPS in LyzM+ myeloid cells and MRP8+ neutrophils, but not CD11c+ cells and IECs, is necessary for bacterial clearance and host survival during intracellular bacterial infection. Thus, we reveal hierarchical cell-type-specific roles of caspase-11 that govern the host-protective and host-detrimental functions of the cytosolic LPS surveillance. [Display omitted] •Macrophage/monocyte-specific caspase-11 plays a dominant detrimental role in sepsis•DC- and intestinal epithelial cell-specific caspase-11 play minor roles in sepsis•Neutrophil-specific caspase-11 is dispensable for lethal LPS shock•Macrophage- and neutrophil-specific caspase-11 confer antibacterial defense Kumari et al. reveal hierarchical cell-type-specific roles of caspase-11 that govern the host-protective and host-detrimental functions of the cytosolic LPS surveillance pathway during bacterial infections and sepsis, respectively.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2211-1247eISSN: 2211-1247DOI: 10.1016/j.celrep.2021.109012Titel-ID: cdi_doaj_primary_oai_doaj_org_article_27b0c47d86434abc9477ce596fec8298
- Format
- –
- Schlagworte
- Animals, bacteria, Burkholderia - growth & development, Burkholderia - pathogenicity, Calgranulin A - genetics, Calgranulin A - immunology, caspase-11, Caspases, Initiator - genetics, Caspases, Initiator - immunology, CD11 Antigens - genetics, CD11 Antigens - immunology, cell death, Dendritic Cells - immunology, Dendritic Cells - microbiology, Epithelial Cells - immunology, Epithelial Cells - microbiology, Female, gasdermin D, Gene Expression Regulation, infection, inflammasome, Interleukin-18 - genetics, Interleukin-18 - immunology, Interleukin-1beta - genetics, Interleukin-1beta - immunology, Lipopolysaccharides - toxicity, Liver - immunology, Liver - microbiology, LPS, Macrophages, Peritoneal - immunology, Macrophages, Peritoneal - microbiology, Male, Mice, Mice, Transgenic, Microfilament Proteins - genetics, Microfilament Proteins - immunology, Monocytes - immunology, Monocytes - microbiology, Neutrophils - immunology, Neutrophils - microbiology, Phosphate-Binding Proteins - genetics, Phosphate-Binding Proteins - immunology, Pore Forming Cytotoxic Proteins - genetics, Pore Forming Cytotoxic Proteins - immunology, pyroptosis, sepsis, Shock, Septic - genetics, Shock, Septic - immunology, Shock, Septic - microbiology, Shock, Septic - mortality, Signal Transduction, Spleen - immunology, Spleen - microbiology, Survival Analysis