Caspase-6 promotes activation of the caspase-11-NLRP3 inflammasome during gram-negative bacterial infections
| Autor: | Balabhaskararao Kancharana, Thirumala-Devi Kanneganti, Min Zheng, Rajendra Karki, Hartmut Berns, Shondra M. Pruett-Miller |
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| Rok vydání: | 2021 |
| Předmět: |
Male
CASP11 caspase-11 Lipopolysaccharide caspase-11 caspase-6 Biochemistry Mice chemistry.chemical_compound ERK extracellular signal-regulated kinase Interferon CARD caspase-activation and recruitment domain NLRP nucleotide-binding oligomerization domain-like receptor containing pyrin domain Cells Cultured NLR nucleotide-binding oligomerization domain-like receptor Caspase 6 biology ASC apoptosis-associated speck-like protein containing a CARD gasdermin D pyroptosis BMDMs bone marrow-derived macrophages Pyroptosis Inflammasome P. aeruginosa gram-negative bacteria Caspases Initiator Cell biology cell death LPS lipopolysaccharide Female Research Article medicine.drug GBP guanylate-binding proteins Gram-negative bacteria C. rodentium Caspase-11 Proinflammatory cytokine NLRP3 inflammasome NLR Family Pyrin Domain-Containing 3 Protein IAV influenza A virus medicine Animals IFN interferon GSDMD gasdermin D Molecular Biology Innate immune system NGS next generation sequencing Cell Biology E. coli biology.organism_classification Mice Inbred C57BL CASP6 caspase-6 chemistry Gram-Negative Bacterial Infections IRGB10 immunity-related GTPase B10 |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| DOI: | 10.1016/j.jbc.2021.101379 |
| Popis: | The innate immune system acts as the first line of defense against infection. One key component of the innate immune response to gram-negative bacterial infections is inflammasome activation. The caspase-11 (CASP11)-nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is activated by cytosolic lipopolysaccharide, a gram-negative bacterial cell wall component, to trigger pyroptosis and host defense during infection. Although several cellular signaling pathways have been shown to regulate CASP11-NLRP3 inflammasome activation in response to lipopolysaccharide, the upstream molecules regulating CASP11 activation during infection with live pathogens remain unclear. Here, we report that the understudied caspase-6 (CASP6) contributes to the activation of the CASP11-NLRP3 inflammasome in response to infections with gram-negative bacteria. Using in vitro cellular systems with bone marrow-derived macrophages and 293T cells, we found that CASP6 can directly process CASP11 by cleaving at Asp59 and Asp285, the CASP11 auto-cleavage sites, which could contribute to the activation of CASP11 during gram-negative bacterial infection. Thus, the loss of CASP6 led to impaired CASP11-NLRP3 inflammasome activation in response to gram-negative bacteria. These results demonstrate that CASP6 potentiates activation of the CASP11-NLRP3 inflammasome to produce inflammatory cytokines during gram-negative bacterial infections. |
| Databáze: | OpenAIRE |
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