Activation of the AIM2 Receptor in Circulating Cells of Post-COVID-19 Patients With Signs of Lung Fibrosis Is Associated With the Release of IL-1α, IFN-α and TGF-β.

Colarusso, C; Terlizzi, M; Maglio, A; Molino, A; Candia, C; Vitale, C; Hansbro, PM; Vatrella, A; Pinto, A; Sorrentino, R

Activation of the AIM2 Receptor in Circulating Cells of Post-COVID-19 Patients With Signs of Lung Fibrosis Is Associated With the Release of IL-1α, IFN-α and TGF-β.

Colarusso, C Terlizzi, M Maglio, A Molino, A Candia, C Vitale, C Hansbro, PM Vatrella, A Pinto, A Sorrentino, R

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Publisher:: FRONTIERS MEDIA SA
Publication Type:: Journal Article
Citation:: Front Immunol, 2022, 13, pp. 934264
Issue Date:: 2022

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Field	Value	Language
dc.contributor.author	Colarusso, C
dc.contributor.author	Terlizzi, M
dc.contributor.author	Maglio, A
dc.contributor.author	Molino, A
dc.contributor.author	Candia, C
dc.contributor.author	Vitale, C
dc.contributor.author	Hansbro, PM
dc.contributor.author	Vatrella, A
dc.contributor.author	Pinto, A
dc.contributor.author	Sorrentino, R
dc.date.accessioned	2023-02-22T04:19:03Z
dc.date.available	2022-05-27
dc.date.available	2023-02-22T04:19:03Z
dc.date.issued	2022
dc.identifier.citation	Front Immunol, 2022, 13, pp. 934264
dc.identifier.issn	1664-3224
dc.identifier.issn	1664-3224
dc.identifier.uri	http://hdl.handle.net/10453/166311
dc.description.abstract	Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), responsible for COVID-19, has caused a global pandemic. Observational studies revealed a condition, herein called as Long-COVID syndrome (PC), that affects both moderately and severely infected patients, reducing quality-of-life. The mechanism/s underlying the onset of fibrotic-like changes in PC are still not well defined. The goal of this study was to understand the involvement of the Absent in melanoma-2 (AIM2) inflammasome in PC-associated lung fibrosis-like changes revealed by chest CT scans. Peripheral blood mononuclear cells (PBMCs) obtained from PC patients who did not develop signs of lung fibrosis were not responsive to AIM2 activation by Poly dA:dT. In sharp contrast, PBMCs from PC patients with signs of lung fibrosis were highly responsive to AIM2 activation, which induced the release of IL-1α, IFN-α and TGF-β. The recognition of Poly dA:dT was not due to the activation of cyclic GMP-AMP (cGAMP) synthase, a stimulator of interferon response (cGAS-STING) pathways, implying a role for AIM2 in PC conditions. The release of IFN-α was caspase-1- and caspase-4-dependent when AIM2 was triggered. Instead, the release of pro-inflammatory IL-1α and pro-fibrogenic TGF-β were inflammasome independent because the inhibition of caspase-1 and caspase-4 did not alter the levels of the two cytokines. Moreover, the responsiveness of AIM2 correlated with higher expression of the receptor in circulating CD14+ cells in PBMCs from patients with signs of lung fibrosis.
dc.format	Electronic-eCollection
dc.language	eng
dc.publisher	FRONTIERS MEDIA SA
dc.relation	http://purl.org/au-research/grants/nhmrc/1175134
dc.relation.ispartof	Front Immunol
dc.relation.isbasedon	10.3389/fimmu.2022.934264
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1107 Immunology, 1108 Medical Microbiology
dc.subject.mesh	COVID-19
dc.subject.mesh	Carrier Proteins
dc.subject.mesh	Caspase 1
dc.subject.mesh	DNA-Binding Proteins
dc.subject.mesh	Humans
dc.subject.mesh	Inflammasomes
dc.subject.mesh	Interferon-alpha
dc.subject.mesh	Leukocytes, Mononuclear
dc.subject.mesh	Pulmonary Fibrosis
dc.subject.mesh	SARS-CoV-2
dc.subject.mesh	Transforming Growth Factor beta
dc.subject.mesh	Post-Acute COVID-19 Syndrome
dc.subject.mesh	Leukocytes, Mononuclear
dc.subject.mesh	Humans
dc.subject.mesh	Pulmonary Fibrosis
dc.subject.mesh	Caspase 1
dc.subject.mesh	Transforming Growth Factor beta
dc.subject.mesh	Carrier Proteins
dc.subject.mesh	DNA-Binding Proteins
dc.subject.mesh	Interferon-alpha
dc.subject.mesh	Inflammasomes
dc.subject.mesh	COVID-19
dc.subject.mesh	SARS-CoV-2
dc.subject.mesh	COVID-19
dc.subject.mesh	Carrier Proteins
dc.subject.mesh	Caspase 1
dc.subject.mesh	DNA-Binding Proteins
dc.subject.mesh	Humans
dc.subject.mesh	Inflammasomes
dc.subject.mesh	Interferon-alpha
dc.subject.mesh	Leukocytes, Mononuclear
dc.subject.mesh	Pulmonary Fibrosis
dc.subject.mesh	SARS-CoV-2
dc.subject.mesh	Transforming Growth Factor beta
dc.title	Activation of the AIM2 Receptor in Circulating Cells of Post-COVID-19 Patients With Signs of Lung Fibrosis Is Associated With the Release of IL-1α, IFN-α and TGF-β.
dc.type	Journal Article
utslib.citation.volume	13
utslib.location.activity	Switzerland
utslib.for	1107 Immunology
utslib.for	1108 Medical Microbiology
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
pubs.organisational-group	/University of Technology Sydney/Strength - CFI - Centre for Inflammation
utslib.copyright.status	open_access	*
dc.date.updated	2023-02-22T04:18:24Z
pubs.publication-status	Published online
pubs.volume	13

Abstract:

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), responsible for COVID-19, has caused a global pandemic. Observational studies revealed a condition, herein called as Long-COVID syndrome (PC), that affects both moderately and severely infected patients, reducing quality-of-life. The mechanism/s underlying the onset of fibrotic-like changes in PC are still not well defined. The goal of this study was to understand the involvement of the Absent in melanoma-2 (AIM2) inflammasome in PC-associated lung fibrosis-like changes revealed by chest CT scans. Peripheral blood mononuclear cells (PBMCs) obtained from PC patients who did not develop signs of lung fibrosis were not responsive to AIM2 activation by Poly dA:dT. In sharp contrast, PBMCs from PC patients with signs of lung fibrosis were highly responsive to AIM2 activation, which induced the release of IL-1α, IFN-α and TGF-β. The recognition of Poly dA:dT was not due to the activation of cyclic GMP-AMP (cGAMP) synthase, a stimulator of interferon response (cGAS-STING) pathways, implying a role for AIM2 in PC conditions. The release of IFN-α was caspase-1- and caspase-4-dependent when AIM2 was triggered. Instead, the release of pro-inflammatory IL-1α and pro-fibrogenic TGF-β were inflammasome independent because the inhibition of caspase-1 and caspase-4 did not alter the levels of the two cytokines. Moreover, the responsiveness of AIM2 correlated with higher expression of the receptor in circulating CD14+ cells in PBMCs from patients with signs of lung fibrosis.

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http://hdl.handle.net/10453/166311