Interferon signalling and non-canonical inflammasome activation promote host protection against multidrug-resistant Acinetobacter baumannii.

Li, F-J; Starrs, L; Mathur, A; Enosi Tuipulotu, D; Man, SM; Burgio, G

Interferon signalling and non-canonical inflammasome activation promote host protection against multidrug-resistant Acinetobacter baumannii.

Li, F-J Starrs, L Mathur, A Enosi Tuipulotu, D

Man, SM Burgio, G

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Publisher:: NATURE PORTFOLIO
Publication Type:: Journal Article
Citation:: Commun Biol, 2024, 7, (1), pp. 1494
Issue Date:: 2024-11-12

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Field	Value	Language
dc.contributor.author	Li, F-J
dc.contributor.author	Starrs, L
dc.contributor.author	Mathur, A
dc.contributor.author	Enosi Tuipulotu, D https://orcid.org/0000-0002-6442-4633
dc.contributor.author	Man, SM
dc.contributor.author	Burgio, G
dc.date.accessioned	2024-12-16T23:21:46Z
dc.date.available	2024-11-04
dc.date.available	2024-12-16T23:21:46Z
dc.date.issued	2024-11-12
dc.identifier.citation	Commun Biol, 2024, 7, (1), pp. 1494
dc.identifier.issn	2399-3642
dc.identifier.issn	2399-3642
dc.identifier.uri	http://hdl.handle.net/10453/182600
dc.description.abstract	Multidrug-resistant (MDR) Acinetobacter baumannii are of major concern worldwide due to their resistance to last resort carbapenem and polymyxin antibiotics. To develop an effective treatment strategy, it is critical to better understand how an A. baumannii MDR bacterium interacts with its mammalian host. Pattern-recognition receptors sense microbes, and activate the inflammasome pathway, leading to pro-inflammatory cytokine production and programmed cell death. Here, we examined the effects of a systemic MDR A. baumannii infection and found that MDR A. baumannii activate the NLRP3 inflammasome complex predominantly via the non-canonical caspase-11-dependent pathway. We show that caspase-1 and caspase-11-deficient mice are protected from a virulent MDR A. baumannii strain by maintaining a balance between protective and deleterious inflammation. Caspase-11-deficient mice also compromise between effector cell recruitment, phagocytosis, and programmed cell death in the lung during infection. Importantly, we found that cytosolic immunity - mediated by guanylate-binding protein 1 (GBP1) and type I interferon signalling - orchestrates caspase-11-dependent inflammasome activation. Together, our results suggest that non-canonical inflammasome activation via the (Interferon) IFN pathway plays a critical role in the host response against MDR A. baumannii infection.
dc.format	Electronic
dc.language	eng
dc.publisher	NATURE PORTFOLIO
dc.relation.ispartof	Commun Biol
dc.relation.isbasedon	10.1038/s42003-024-07204-3
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.classification	31 Biological sciences
dc.subject.classification	32 Biomedical and clinical sciences
dc.subject.mesh	Acinetobacter baumannii
dc.subject.mesh	Animals
dc.subject.mesh	Inflammasomes
dc.subject.mesh	Acinetobacter Infections
dc.subject.mesh	Drug Resistance, Multiple, Bacterial
dc.subject.mesh	Mice
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Caspases, Initiator
dc.subject.mesh	Mice, Inbred C57BL
dc.subject.mesh	Mice, Knockout
dc.subject.mesh	Caspases
dc.subject.mesh	Caspase 1
dc.subject.mesh	NLR Family, Pyrin Domain-Containing 3 Protein
dc.subject.mesh	Animals
dc.subject.mesh	Mice, Inbred C57BL
dc.subject.mesh	Mice, Knockout
dc.subject.mesh	Mice
dc.subject.mesh	Acinetobacter baumannii
dc.subject.mesh	Acinetobacter Infections
dc.subject.mesh	Caspases
dc.subject.mesh	Caspase 1
dc.subject.mesh	Drug Resistance, Multiple, Bacterial
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Caspases, Initiator
dc.subject.mesh	Inflammasomes
dc.subject.mesh	NLR Family, Pyrin Domain-Containing 3 Protein
dc.subject.mesh	Acinetobacter baumannii
dc.subject.mesh	Animals
dc.subject.mesh	Inflammasomes
dc.subject.mesh	Acinetobacter Infections
dc.subject.mesh	Drug Resistance, Multiple, Bacterial
dc.subject.mesh	Mice
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Caspases, Initiator
dc.subject.mesh	Mice, Inbred C57BL
dc.subject.mesh	Mice, Knockout
dc.subject.mesh	Caspases
dc.subject.mesh	Caspase 1
dc.subject.mesh	NLR Family, Pyrin Domain-Containing 3 Protein
dc.title	Interferon signalling and non-canonical inflammasome activation promote host protection against multidrug-resistant Acinetobacter baumannii.
dc.type	Journal Article
utslib.citation.volume	7
utslib.location.activity	England
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2024-12-16T23:21:43Z
pubs.issue	1
pubs.publication-status	Published online
pubs.volume	7
utslib.citation.issue	1

Abstract:

Multidrug-resistant (MDR) Acinetobacter baumannii are of major concern worldwide due to their resistance to last resort carbapenem and polymyxin antibiotics. To develop an effective treatment strategy, it is critical to better understand how an A. baumannii MDR bacterium interacts with its mammalian host. Pattern-recognition receptors sense microbes, and activate the inflammasome pathway, leading to pro-inflammatory cytokine production and programmed cell death. Here, we examined the effects of a systemic MDR A. baumannii infection and found that MDR A. baumannii activate the NLRP3 inflammasome complex predominantly via the non-canonical caspase-11-dependent pathway. We show that caspase-1 and caspase-11-deficient mice are protected from a virulent MDR A. baumannii strain by maintaining a balance between protective and deleterious inflammation. Caspase-11-deficient mice also compromise between effector cell recruitment, phagocytosis, and programmed cell death in the lung during infection. Importantly, we found that cytosolic immunity - mediated by guanylate-binding protein 1 (GBP1) and type I interferon signalling - orchestrates caspase-11-dependent inflammasome activation. Together, our results suggest that non-canonical inflammasome activation via the (Interferon) IFN pathway plays a critical role in the host response against MDR A. baumannii infection.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/182600