Pathogenic ubiquitination of GSDMB inhibits NK cell bactericidal functions
| Autor: | Li-Shu Zhang, Qi Wu, Justin M. Hansen, Maarten F. de Jong, David B. Heisler, Laura Taylor Alto, Neal M. Alto |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Pore Forming Cytotoxic Proteins
Proteasome Endopeptidase Complex Cardiolipins Virulence Mice Transgenic General Biochemistry Genetics and Molecular Biology Article Granzymes Microbiology Cell Line Shigella flexneri Substrate Specificity 03 medical and health sciences 0302 clinical medicine Ubiquitin Bacterial Proteins medicine Biomarkers Tumor Animals Humans 030304 developmental biology 0303 health sciences Innate immune system Microbial Viability biology Effector Cell Membrane Ubiquitination Inflammasome biology.organism_classification Research Highlight Ubiquitin ligase Neoplasm Proteins Killer Cells Natural Mice Inbred C57BL Lipid A Proteasome Host-Pathogen Interactions Proteolysis biology.protein Female 030217 neurology & neurosurgery medicine.drug Protein Binding |
| Zdroj: | Cell Res Cell |
| ISSN: | 1097-4172 |
| Popis: | Gasdermin B (GSDMB) belongs to a large family of pore forming cytolysins that execute inflammatory cell death programs. While genetic studies have linked GSDMB polymorphisms to human disease, its function in the immunological response to pathogens remains poorly understood. Here, we report a dynamic host-pathogen conflict between GSDMB and the IpaH7.8 effector protein secreted by enteroinvasive Shigella flexneri. We show that IpaH7.8 ubiquitinates and targets GSDMB for 26S proteasome destruction. This virulence strategy protects Shigella from the bacteriocidic activity of Natural Killer cells by suppressing Granzyme-A mediated activation of GSDMB. In contrast to the canonical function of most Gasdermin-family members, GSDMB does not inhibit Shigella by lysing host cells. Rather, it exhibits direct microbiocidal activity through recognition of phospholipids found on Gram-negative bacterial membranes. These findings place GSDMB as a central executioner of intracellular bacterial killing and reveals a mechanism employed by pathogens to counteract this host defense system. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|