Evidence map›Paper›PMID 40733745›Full record

ArticleVaccines2025

Immunization with Complete Freund's Adjuvant Reveals Trained Immunity-like Features in A/J Mice.

Kiruthiga Mone, Shraddha Singh, Fatema Abdullatif, Meghna Sur, Mahima T Rasquinha, Javier Seravalli, Denise K Zinniel, Indranil Mukhopadhyay, Raul G Barletta, Teklab Gebregiworgis and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Vaccines, 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. Article
  2. Article
  3. Article
  4. 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

11 authors.

Kiruthiga MoneSchool of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.ORCID 0000-0003-0379-4152
Shraddha SinghSchool of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
Fatema AbdullatifDepartment of Biochemistry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada.ORCID 0009-0004-4288-8914
Meghna SurSchool of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
Mahima T RasquinhaSchool of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.ORCID 0000-0003-0923-4869
Javier SeravalliDepartment of Biochemistry, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
Denise K ZinnielSchool of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.ORCID 0009-0007-5421-9461
Indranil MukhopadhyayDepartment of Statistics, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
Raul G BarlettaSchool of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.ORCID 0000-0002-2278-2563
Teklab GebregiworgisDepartment of Biochemistry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada.ORCID 0000-0002-1489-4813
Jay ReddySchool of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.ORCID 0000-0003-4082-9254

Funding

Trained immunity in the prevention of viral myocarditis and pancreatitisR21AI166773 · NIAID · UNIVERSITY OF NEBRASKA LINCOLN · PI REDDY, JAY · 2022 to 2023
$398k
NIAID NIH HHS R21 AI166773NIH HHS 1R21AI166773-24
6 · The paper itself

Abstract

BACKGROUND/

objectivesFreund's adjuvants induce different immunomodulatory effects, but their underlying molecular mechanisms are unclear. In this study, we investigated whether the immune-stimulating effects of the complete Freund's adjuvant (CFA) involve the mechanisms of trained immunity (TI).

methodsWe examined bone marrow cells (BMCs) isolated from CFA-immunized A/J mice to address this question. Incomplete Freund's adjuvant (IFA) and

resultsFirst, BMCs from all groups except saline showed varied levels of IL-1β, IL-6, and TNF-α. But expression of CCL5 and CXCL10 was significantly elevated only in the CFA and BCG groups. Transcriptionally, significant elevations were noted for TNF-α and IL-1β in the CFA and BCG groups, whereas CXCL10, IL-6, and IL-10 were upregulated in the CFA and BCG groups, respectively. Second, while BMCs from the BCG group expressed the markers of both the M1 and M2 macrophages, no clear trends were noted in the CFA and IFA groups. Third, cell lysates from the CFA group revealed metabolic reprogramming in the BMCs. Specifically, we observed an increased level of lactate, indicative of aerobic glycolysis, which is implicated in TI, and this was also detected in the IFA group. Fourth, epigenetic analysis revealed histone enrichment in the promoter region of TNF-α, in the CFA group, but to a lesser degree than the BCG group. However, no epigenetic changes were observed in the IFA group.

conclusionsOur data provide new insights into the mechanisms of Freund's adjuvants and the immunomodulatory effects of CFA could involve the features of TI.

Indexed as

adjuvantsCFAcomplete Freund’s adjuvantepigeneticsFreund’s adjuvantsIFAimmunometabolismincomplete Freund’s adjuvantinnate immune memorymetabolomicstrained immunityvaccine adjuvants

Identifiers

PMID40733745
PMCPMC12300380

What Socratic 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 Socratic graph.