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Journal article
Immunity against Moraxella catarrhalis requires guanylate-binding proteins and caspase-11-NLRP3 inflammasomes
The EMBO journal, Vol.42(6), Art. e112558
2023
PMID: 36762431
Abstract
Moraxella catarrhalis is an important human respiratory pathogen and a major causative agent of otitis media and chronic obstructive pulmonary disease. Toll-like receptors contribute to, but cannot fully account for, the complexity of the immune response seen in M. catarrhalis infection. Using primary mouse bone marrow-derived macrophages to examine the host response to M. catarrhalis infection, our global transcriptomic and targeted cytokine analyses revealed activation of immune signalling pathways by both membrane-bound and cytosolic pattern-recognition receptors. We show that M. catarrhalis and its outer membrane vesicles or lipooligosaccharide (LOS) can activate the cytosolic innate immune sensor caspase-4/11, gasdermin-D-dependent pyroptosis, and the NLRP3 inflammasome in human and mouse macrophages. This pathway is initiated by type I interferon signalling and guanylate-binding proteins (GBPs). We also show that inflammasomes and GBPs, particularly GBP2, are required for the host defence against M. catarrhalis in mice. Overall, our results reveal an essential role for the interferon-inflammasome axis in cytosolic recognition and immunity against M. catarrhalis, providing new molecular targets that may be used to mitigate pathological inflammation triggered by this pathogen.
Details
- Title
- Immunity against Moraxella catarrhalis requires guanylate-binding proteins and caspase-11-NLRP3 inflammasomes
- Authors/Creators
- Daniel Enosi Tuipulotu - Supreme Council Of HealthShouya Feng - Australian National UniversityAbhimanu Pandey - Australian National UniversityAnyang Zhao - Australian National UniversityChinh Ngo - Australian National UniversityAnukriti Mathur - Australian National UniversityJiwon Lee - Australian National UniversityCheng Shen - Australian National UniversityDaniel Fox - Australian National UniversityYansong Xue - Australian National UniversityCallum Kay - Australian National UniversityMax Kirkby - Australian National UniversityJordan Lo Pilato - Supreme Council Of HealthNadeem O. Kaakoush - UNSW SydneyDaryl Webb - Australian National UniversityMelanie Rug - Australian National UniversityAvril A. B. Robertson - The University of QueenslandMelkamu B. Tessema - Peter Doherty InstituteStanley Pang - Murdoch University, Centre for Biosecurity and One HealthDaniel Degrandi - Heinrich Heine University DüsseldorfKlaus Pfeffer - Heinrich Heine University DüsseldorfDaria Augustyniak - University of WrocławAntje Blumenthal - The University of QueenslandLisa A. Miosge - Australian National UniversityAnne Brustle - Australian National UniversityMasahiro Yamamoto - The University of OsakaPatrick C. Reading - Peter Doherty InstituteGaetan Burgio - Australian National UniversitySi Ming Man - Australian National University
- Publication Details
- The EMBO journal, Vol.42(6), Art. e112558
- Publisher
- Wiley
- Number of pages
- 24
- Grant note
- CSL Centenary Fellowship Gastroenterology Society of Australia Mostyn Family Grant National Collaborative Research Infrastructure Strategy (NCRIS) via Phenomics Australia - Gastroenterology Society of Australia Mostyn Family Grant Australian National University APP1141504; APP1146864; APP1162103; APP1163358 / John Curtin School of Medical Research PhD Scholarship University and the Federal Government John Curtin School of Medical Research PhD Scholarship Gretel and Gordon Bootes Medical Research Foundation Federal Government National Health and Medical Research Council of Australia; National Health and Medical Research Council (NHMRC) of Australia
- Identifiers
- 991005567367007891
- Copyright
- © 2023 The Authors.
- Murdoch Affiliation
- Centre for Biosecurity and One Health
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.6 Immunology
- 1.6.609 Toll-like Receptors
- Web Of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- ESI research areas
- Molecular Biology & Genetics