Cell, 2018-05, Vol.173 (4), p.920-933.e13
2018
Details
- Autor(en) / Beteiligte
- Titel
- IRF8 Regulates Transcription of Naips for NLRC4 Inflammasome Activation
- Ist Teil von
- Cell, 2018-05, Vol.173 (4), p.920-933.e13
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2018
- Link zum Volltext
- Quelle
- Electronic Journals Library - Freely accessible e-journals
- Beschreibungen/Notizen
- Inflammasome activation is critical for host defenses against various microbial infections. Activation of the NLRC4 inflammasome requires detection of flagellin or type III secretion system (T3SS) components by NLR family apoptosis inhibitory proteins (NAIPs); yet how this pathway is regulated is unknown. Here, we found that interferon regulatory factor 8 (IRF8) is required for optimal activation of the NLRC4 inflammasome in bone-marrow-derived macrophages infected with Salmonella Typhimurium, Burkholderia thailandensis, or Pseudomonas aeruginosa but is dispensable for activation of the canonical and non-canonical NLRP3, AIM2, and Pyrin inflammasomes. IRF8 governs the transcription of Naips to allow detection of flagellin or T3SS proteins to mediate NLRC4 inflammasome activation. Furthermore, we found that IRF8 confers protection against bacterial infection in vivo, owing to its role in inflammasome-dependent cytokine production and pyroptosis. Altogether, our findings suggest that IRF8 is a critical regulator of NAIPs and NLRC4 inflammasome activation for defense against bacterial infection. [Display omitted] •IRF8 is required for the optimal activation of NLRC4 inflammasome•The expression of Naip1, Naip2, Naip5, and Naip6 is dependent on IRF8•IRF8 is dispensable for the activation of NLRP3, AIM2, and Pyrin inflammasomes•Irf8–/– mice are susceptible to S. Typhimurium and B. thailandensis infection Optimal activation of NLRC4 inflammasome in response to pathogenic bacteria is dependent on IRF8.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0092-8674eISSN: 1097-4172DOI: 10.1016/j.cell.2018.02.055Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5935577
- Format
- –
- Schlagworte
- Animals, Apoptosis Regulatory Proteins - genetics, Apoptosis Regulatory Proteins - metabolism, Burkholderia, Calcium-Binding Proteins - genetics, Calcium-Binding Proteins - metabolism, caspase-1, Cells, Cultured, Cytokines - metabolism, Electrophoretic Mobility Shift Assay, Flagellin - metabolism, ICSBP, inflammasome, Inflammasomes - metabolism, Interferon Regulatory Factors - antagonists & inhibitors, Interferon Regulatory Factors - genetics, Interferon Regulatory Factors - metabolism, IRF8, Macrophages - cytology, Macrophages - metabolism, Macrophages - microbiology, Mice, NAIP, Neuronal Apoptosis-Inhibitory Protein - genetics, Neuronal Apoptosis-Inhibitory Protein - metabolism, NLR, NLR Family, Pyrin Domain-Containing 3 Protein - genetics, NLR Family, Pyrin Domain-Containing 3 Protein - metabolism, NLRC4, Promoter Regions, Genetic, Protein Binding, Pseudomonas aeruginosa - pathogenicity, PU.1, Pyroptosis, RNA Interference, RNA, Small Interfering - metabolism, Salmonella, Salmonella typhimurium - pathogenicity, Transcription, Genetic