Evidence map›Paper›PMID 35512020›Full record

ArticlePLoS pathogens2022

Type I interferon regulates proteolysis by macrophages to prevent immunopathology following viral infection.

Amanda J Lee, Emily Feng, Marianne V Chew, Elizabeth Balint, Sophie M Poznanski, Elizabeth Giles, Ali Zhang, Art Marzok, Spencer D Revill, Fatemeh Vahedi and 12 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.7field-weighted citation impact, top 34% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 10 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 4 institutions in 2 countries.

Amanda J LeeDepartment of Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
Emily FengDepartment of Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.ORCID 0000-0002-1109-4749
Marianne V ChewDepartment of Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.ORCID 0000-0002-5960-5034
Elizabeth BalintDepartment of Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.ORCID 0000-0001-6310-7807
Sophie M PoznanskiDepartment of Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
Elizabeth GilesDepartment of Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.ORCID 0000-0002-1104-3319
Ali ZhangDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Art MarzokDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.ORCID 0000-0002-7112-6853
Spencer D RevillDepartment of Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.ORCID 0000-0003-2165-5228
Fatemeh VahediDepartment of Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.ORCID 0000-0001-7377-2835
Anisha DubeyDepartment of Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
Ehab AyaubDepartment of Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
Rodrigo Jimenez-SaizDepartment of Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.ORCID 0000-0002-0606-3251
Joshua J C McGrathDepartment of Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
Tyrah M RitchieDepartment of Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
Manel JordanaDepartment of Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
Danny D JonigkInstitute of Pathology, Hannover Medical School, Member of the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany.ORCID 0000-0002-5251-2281
Maximilian AckermannInstitute of Pathology and Molecular Pathology, Helios University Clinic Wuppertal, University of Witten/Herdecke, Wuppertal, Germany.ORCID 0000-0001-9996-2477
Kjetil AskDepartment of Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
Matthew MillerDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Carl D RichardsDepartment of Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
Ali A AshkarDepartment of Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.ORCID 0000-0003-1139-1468
McMaster University Medical Centre · CAMcMaster University · CAJohannes Gutenberg University Mainz · DEMedizinische Hochschule Hannover · DE

Funding

CIHR 20008285
6 · The paper itself

Abstract

The ability to treat severe viral infections is limited by our understanding of the mechanisms behind virus-induced immunopathology. While the role of type I interferons (IFNs) in early control of viral replication is clear, less is known about how IFNs can regulate the development of immunopathology and affect disease outcomes. Here, we report that absence of type I IFN receptor (IFNAR) is associated with extensive immunopathology following mucosal viral infection. This pathology occurred independent of viral load or type II immunity but required the presence of macrophages and IL-6. The depletion of macrophages and inhibition of IL-6 signaling significantly abrogated immunopathology. Tissue destruction was mediated by macrophage-derived matrix metalloproteinases (MMPs), as MMP inhibition by doxycycline and Ro 28-2653 reduced the severity of tissue pathology. Analysis of post-mortem COVID-19 patient lungs also displayed significant upregulation of the expression of MMPs and accumulation of macrophages. Overall, we demonstrate that IFNs inhibit macrophage-mediated MMP production to prevent virus-induced immunopathology and uncover MMPs as a therapeutic target towards viral infections.

Indexed as

COVID-19Interferon Type IOrthomyxoviridae InfectionsHumansInterleukin-6MacrophagesProteolysisInterferon Type IInterleukin-6

Identifiers

PMID35512020
PMCPMC9113601
OpenAlexW4229042432

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.