Evidence map›Paper›PMID 42770296›Full record

ArticleJCI insight2026

Caspase-11-mediated hyperinflammation impairs CD8+ T cell immunity and viral clearance in severe SARS-CoV-2 infection.

Mostafa M Eltobgy, Mohamed M Shamseldin, Owen D Whitham, Heba M Amer, Jeffrey R Atkinson, Asmaa Badr, Jesse M Hall, Gauruv Gupta, Yara Y Hassan, Rabab El-Mergawy and 25 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

35 authors.

Mostafa M EltobgyDepartment of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Mohamed M ShamseldinDepartment of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Owen D WhithamDepartment of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Heba M AmerDepartment of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Jeffrey R AtkinsonDepartment of Neurology, College of Medicine and Wexner Medical Center.
Asmaa BadrDepartment of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Jesse M HallDepartment of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Gauruv GuptaDepartment of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Yara Y HassanDepartment of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Rabab El-MergawyDepartment of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Richard PerezDepartment of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Sarah E FaberDepartment of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Maciej PietrzakDepartment of Biomedical Informatics, The Ohio State University, Columbus, Ohio, USA.
Amy WebbDepartment of Biomedical Informatics, The Ohio State University, Columbus, Ohio, USA.
Xiaoli ZhangCollege of Nursing, University of South Florida, Tampa, Florida, USA.
Adam D KenneyDepartment of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Destiny BissellDepartment of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Jihad I OmranDepartment of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Shady EstfanousDepartment of Microbiology and Immunology, Faculty of Pharmacy, Helwan University, Cairo, Egypt.
Kylene P DailyDepartment of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Amir YousifDepartment of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Marisa R JoldrichsenDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA.
Andrew McNamaraDepartment of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Mahesh KcAbigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Mark E PeeplesAbigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Emily A HemannDepartment of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Hazem E GhoneimDepartment of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Shahid M NimjeeDepartment of Neurological Surgery, College of Medicine and Wexner Medical Center, The Ohio State University, Columbus, Ohio, USA.
Estelle Cormet-BoyakaDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA.
Jianrong LiDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA.
Prosper N BoyakaDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA.
Jacob S YountDepartment of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Benjamin M SegalDepartment of Neurology, College of Medicine and Wexner Medical Center.
Purnima DubeyDepartment of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Amal O AmerDepartment of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio, USA.

Funding

Role of the Non-canonical Inflammasome in SARS-CoV-2-mediated Pathology and CoagulopathyP01AI175399 · NIAID · OHIO STATE UNIVERSITY · PI Amal O Amer, Estelle A Cormet-Boyaka · 2024 to 2026
$12.0M
cGMP Manufacture, Fill-Finish, Release, Analytical and Stability Testing and Stability Program of a Nanoparticle Based HIV Envelope Vaccine75N93022D00005 · NIAID · INTERNATIONAL AIDS VACCINE INITIATIVE · PI HASSELL, THOMAS · 2022 to 2025
$8.0M
Task Area A shall encompass annual follow-up of cohort members, clinical events investigations, study operations, and data analysis and manuscript writing. If implemented, Task A.1 will provide fundin75N92020D00005 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WATSON, KAROL E · 2020 to 2025
$5.1M
NHLBI NIH HHS 75N92020D00005NIAID NIH HHS 75N93022D00005NIAID NIH HHS P01 AI175399NIDA NIH HHS 75N95020D00005NIH HHS 75N93023D00005NIH HHS 75N99020D00005
6 · The paper itself

Abstract

Severe SARS-CoV-2 infection is characterized by lung hyperinflammation, impaired IFN responses, and defective T cell activation, yet the molecular drivers of these immune dysregulations remain incompletely understood. Caspase-11 (CASP11), a key effector of the noncanonical inflammasome, has been shown to mediate an innate hyperinflammatory response and cytokine release in a mild SARS-CoV-2 infection model. However, the role played by CASP11 in severe SARS-CoV-2 disease and how it affects adaptive immunity has not been identified. Here, we found that CASP11 exacerbates severe SARS-CoV-2 pathogenesis by amplifying early innate immune responses while concurrently impairing antiviral CD8+ T cell immunity. Using global KO mice, hematopoietic BM chimeras, and Cx3cr1-expressing mononuclear phagocyte system cell-specific CASP11 deletion models, we show that targeting CASP11 reduces lung inflammation, promotes early NK cell-mediated IFN-γ production, and enhances robust virus-specific effector CD8+ T cell responses. This was associated with enhanced viral clearance and improved survival, even under lethal infection conditions. Importantly, CASP11-KO mice also exhibited faster resolution of postviral inflammation. These findings position CASP11 as a promising immunomodulatory target for acute and delayed manifestations of severe SARS-CoV-2 infection.

Indexed as

CaspasesCaspases, InitiatorCD8-Positive T-LymphocytesCoronavirus InfectionsCOVID-19Adaptive ImmunityAnimalsDisease Models, AnimalFemaleHumansImmunity, InnateInflammationInterferon-gammaKiller Cells, NaturalLungMiceCasp4 protein, mouseCaspasesCaspases, InitiatorInterferon-gammaAdaptive immunityCOVID-19ImmunologyInfectious diseaseInflammationInnate immunity

Identifiers

PMID42770296
PMCPMC13596723

What OpenQuestion holds

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Registered trials

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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.