Evidence map›Paper›PMID 40048372›Full record

ArticleThe Journal of clinical investigation2025

IL-33 protects from recurrent C. difficile infection by restoration of humoral immunity.

Farha Naz, Md Jashim Uddin, Nicholas Hagspiel, Mary K Young, David Tyus, Rachel Boone, Audrey C Brown, Girija Ramakrishnan, Isaura Rigo, Claire Fleming and 2 more

Abstract read
In one paragraph

Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Farha NazDepartment of Medicine, Division of Infectious Diseases and International Health.
Md Jashim UddinDepartment of Medicine, Division of Infectious Diseases and International Health.
Nicholas HagspielDepartment of Medicine, Division of Infectious Diseases and International Health.
Mary K YoungDepartment of Medicine, Division of Infectious Diseases and International Health.
David TyusDepartment of Medicine, Division of Infectious Diseases and International Health.
Rachel BooneDepartment of Microbiology, Immunology, and Cancer Biology, and.
Audrey C BrownDepartment of Medicine, Division of Infectious Diseases and International Health.
Girija RamakrishnanDepartment of Medicine, Division of Infectious Diseases and International Health.
Isaura RigoDepartment of Medicine, Division of Infectious Diseases and International Health.
Claire FlemingDepartment of Medicine, Division of Infectious Diseases and International Health.
Gregory R MaddenDepartment of Medicine, Division of Infectious Diseases and International Health.
William A PetriDepartment of Medicine, Division of Infectious Diseases and International Health.

Funding

Role of Th17 in Severe and Recurrent C. difficile InfectionR01AI152477 · NIAID · UNIVERSITY OF VIRGINIA · PI PETRI, WILLIAM A, RAMAKRISHNAN, GIRIJA · 2020 to 2025
$7.1M
Role of Type 2 Immunity in Innate Protection from C. difficileR01AI124214 · NIAID · UNIVERSITY OF VIRGINIA · PI William A Petri · 2016 to 2026
$5.4M
Role of Hyaluronan in IL-13-mediated COVID-19 PathologyR01HL171283 · NHLBI · UNIVERSITY OF VIRGINIA · PI William A Petri, Jie Sun · 2024 to 2026
$1.9M
Immune profiling to stratify Clostridioides difficile infection outcomesK23AI163368 · NIAID · UNIVERSITY OF VIRGINIA · PI MADDEN, GREGORY RUSSELL · 2021 to 2025
$961k
NHLBI NIH HHS R01 HL171283NIAID NIH HHS K23 AI163368NIAID NIH HHS R01 AI124214NIAID NIH HHS R01 AI152477
6 · The paper itself

Abstract

Clostridioides difficile infection (CDI) recurs in 1 of 5 patients. Monoclonal antibodies targeting the virulence factor TcdB reduce disease recurrence, suggesting that an inadequate anti-TcdB response to CDI leads to recurrence. In patients with CDI, we discovered that IL-33 measured at diagnosis predicts future recurrence, leading us to test the role of IL-33 signaling in the induction of humoral immunity during CDI. Using a mouse recurrence model, IL-33 was demonstrated to be integral for anti-TcdB antibody production. IL-33 acted via ST2+ ILC2 cells, facilitating germinal center T follicular helper (GC-Tfh) cell generation of antibodies. IL-33 protection from reinfection was antibody-dependent, as μMT KO mice and mice treated with anti-CD20 mAb were not protected. These findings demonstrate the critical role of IL-33 in generating humoral immunity to prevent recurrent CDI.

Indexed as

Clostridioides difficileClostridium InfectionsImmunity, HumoralInterleukin-33AnimalsAntibodies, BacterialBacterial ProteinsBacterial ToxinsFemaleHumansInterleukin-1 Receptor-Like 1 ProteinMaleMiceMice, KnockoutRecurrenceT Follicular Helper CellsAntibodies, BacterialBacterial ProteinsBacterial ToxinsIl1rl1 protein, mouseIL33 protein, humanIl33 protein, mouseInterleukin-1 Receptor-Like 1 ProteinInterleukin-33toxB protein, Clostridium difficileAdaptive immunityImmunologyInfectious disease

Identifiers

PMID40048372
PMCPMC12043089

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.