Evidence map›Paper›PMID 34899695›Full record

ArticleFrontiers in immunology2021

Interferon Lambda Signaling in Macrophages Is Necessary for the Antiviral Response to Influenza.

Rama K Mallampalli, Jessica Adair, Ajit Elhance, Daniela Farkas, Lexie Chafin, Matthew E Long, Mithu De, Ana L Mora, Mauricio Rojas, Victor Peters and 3 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
3.2field-weighted citation impact, top 7% 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

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Interferon-JAK-STAT Axis in Bone Metabolism.Current osteoporosis reports · 2026
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  5. The role ofFrontiers in immunology · 2026
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  7. CombinedInternational journal of molecular sciences · 2025
    Article
  8. Review
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  13. Article
  14. Article
  15. Article
  16. Diverging patterns in innate immunity against respiratory viruses during a lifetime: lessons from the young and the old.European respiratory review : an official journal of the European Respiratory Society · 2024
    Review
  17. Ly6CCell reports · 2024
    Article
  18. Review
  19. Influenza virus reduces ubiquitin E3 ligase MARCH10 expression to decrease ciliary beat frequency.American journal of physiology. Lung cellular and molecular physiology · 2023
    Article
  20. Article
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

13 authors at 2 institutions in 1 country.

Rama K MallampalliDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Davis Heart and Lung Research Institute, Columbus, Ohio, United States.
Jessica AdairDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Davis Heart and Lung Research Institute, Columbus, Ohio, United States.
Ajit ElhanceDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Davis Heart and Lung Research Institute, Columbus, Ohio, United States.
Daniela FarkasDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Davis Heart and Lung Research Institute, Columbus, Ohio, United States.
Lexie ChafinDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Davis Heart and Lung Research Institute, Columbus, Ohio, United States.
Matthew E LongDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Davis Heart and Lung Research Institute, Columbus, Ohio, United States.
Mithu DeDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Davis Heart and Lung Research Institute, Columbus, Ohio, United States.
Ana L MoraDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Davis Heart and Lung Research Institute, Columbus, Ohio, United States.
Mauricio RojasDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Davis Heart and Lung Research Institute, Columbus, Ohio, United States.
Victor PetersDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Davis Heart and Lung Research Institute, Columbus, Ohio, United States.
Joseph S BednashDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Davis Heart and Lung Research Institute, Columbus, Ohio, United States.
MuChun TsaiDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Davis Heart and Lung Research Institute, Columbus, Ohio, United States.
James D LondinoDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Davis Heart and Lung Research Institute, Columbus, Ohio, United States.
Sutter Davis Hospital · USThe Ohio State University Wexner Medical Center · US

Funding

Regulation of Cardiolin Byosynthesis in Epithelial InjuryP01HL114453 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MALLAMPALLI, RAMA K · 2014 to 2023
$21.3M
TNF-alpha Control of a Surfactant Enzyme in Lung InjuryR01HL081784 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MALLAMPALLI, RAMA K · 2006 to 2024
$5.4M
F box-Induced Acute Lung Injury and ParkinR01HL096376 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MALLAMPALLI, RAMA K · 2010 to 2025
$5.1M
Sepsis-Associated Immune Suppression and F-box ProteinsR01HL097376 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MALLAMPALLI, RAMA K · 2009 to 2025
$5.1M
A New Genus of Ubiquitin-Based Anti-inflammatories for COPDUH3HL123502 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MALLAMPALLI, RAMA K · 2016 to 2018
$4.6M
Stabilizing mitochondria in sepsisR01HL098174 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MALLAMPALLI, RAMA K · 2010 to 2021
$3.6M
NHLBI NIH HHS P01 HL114453NHLBI NIH HHS R01 HL081784NHLBI NIH HHS R01 HL096376NHLBI NIH HHS R01 HL097376NHLBI NIH HHS R01 HL098174NHLBI NIH HHS UH3 HL123502
6 · The paper itself

Abstract

Interferon lambda (IFNλ) signaling is a promising therapeutic target against viral infection in murine models, yet little is known about its molecular regulation and its cognate receptor, interferon lambda receptor 1 (IFNLR1) in human lung. We hypothesized that the IFNλ signaling axis was active in human lung macrophages. In human alveolar macrophages (HAMs), we observed increased IFNLR1 expression and robust increase in interferon-stimulated gene (ISG) expression in response to IFNλ ligand. While human monocytes express minimal IFNLR1, differentiation of monocytes into macrophages with macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) increased IFNLR1 mRNA, IFNLR1 protein expression, and cellular response to IFNλ ligation. Conversely, in mice, M-CSF or GM-CSF stimulated macrophages failed to produce ISGs in response to related ligands, IFNL2 or IFNL3, suggesting that IFNLR1 signaling in macrophages is species-specific. We next hypothesized that IFNλ signaling was critical in influenza antiviral responses. In primary human airway epithelial cells and precision-cut human lung slices, influenza infection substantially increased IFNλ levels. Pretreatment of both HAMs and differentiated human monocytes with IFNL1 significantly inhibited influenza infection. IFNLR1 knockout in the myeloid cell line, THP-1, exhibited reduced interferon responses to either direct or indirect exposure to influenza infection suggesting the indispensability of IFNLR1 for antiviral responses. These data demonstrate the presence of IFNλ - IFNLR1 signaling axis in human lung macrophages and a critical role of IFNλ signaling in combating influenza infection.

Indexed as

AnimalsCells, CulturedHumansInfluenza, HumanInterferon LambdaInterferonsMacrophages, AlveolarMiceReceptors, InterferonSignal TransductionInterferon LambdaInterferonsReceptors, InterferonGMCSFIFNLR1influenzainterferon lambdalungmacrophageMCSF

Identifiers

PMID34899695
PMCPMC8655102
OpenAlexW3217327507

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.