Evidence map›Paper›PMID 25955764›Full record

ArticlePLoS neglected tropical diseases2015

Deletion of Fibrinogen-like Protein 2 (FGL-2), a Novel CD4+ CD25+ Treg Effector Molecule, Leads to Improved Control of Echinococcus multilocularis Infection in Mice.

Junhua Wang, Dominique A Vuitton, Norbert Müller, Andrew Hemphill, Markus Spiliotis, Oleg Blagosklonov, Denis Grandgirard, Stephen L Leib, Itay Shalev, Gary Levy and 4 more

Open access · goldAbstract read
In one paragraph

Article in PLoS neglected tropical diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.1field-weighted citation impact, top 9% 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

31 citing papers in PubMed, 54 citations in OpenAlex.

  1. Review
  2. Article
  3. Innate Immune Response to Helminth Infections.Advances in experimental medicine and biology · 2025
    Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. sFgl2-Treg Positive Feedback Pathway Protects against Atherosclerosis.International journal of molecular sciences · 2023
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Echinococcosis: Advances in the 21st Century.Clinical microbiology reviews · 2019
    Review
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

14 authors at 6 institutions in 4 countries.

Junhua WangInstitute of Parasitology, University of Bern, Bern, Switzerland; State Key Lab Incubation Base of Xinjiang Major Diseases Research (2010DS890294) and Xinjiang Key Laboratory of Echinococcosis, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China; Department of Nuclear Medicine, University of Franche-Comté and Jean Minjoz University Hospital, Besançon, Franche-Comté, France.
Dominique A VuittonWorld Health Organization (WHO)-Collaborating Centre for the Prevention and Treatment of Human Echinococcosis, University of Franche-Comté and University Hospital, Besançon, Franche-Comté, France.
Norbert MüllerInstitute of Parasitology, University of Bern, Bern, Switzerland.
Andrew HemphillInstitute of Parasitology, University of Bern, Bern, Switzerland.
Markus SpiliotisInstitute of Parasitology, University of Bern, Bern, Switzerland.
Oleg BlagosklonovDepartment of Nuclear Medicine, University of Franche-Comté and Jean Minjoz University Hospital, Besançon, Franche-Comté, France.
Denis GrandgirardNeuroinfection Laboratory, Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
Stephen L LeibNeuroinfection Laboratory, Institute for Infectious Diseases, University of Bern, Bern, Switzerland; Biology Division, Spiez Laboratory, Federal Office for Civil Protection (FOCP), Spiez, Switzerland.
Itay ShalevUniversity of Toronto Transplantation Institute, Toronto, Ontario, Canada.
Gary LevyUniversity of Toronto Transplantation Institute, Toronto, Ontario, Canada.
Xiaomei LuState Key Lab Incubation Base of Xinjiang Major Diseases Research (2010DS890294) and Xinjiang Key Laboratory of Echinococcosis, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
Renyong LinState Key Lab Incubation Base of Xinjiang Major Diseases Research (2010DS890294) and Xinjiang Key Laboratory of Echinococcosis, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
Hao WenState Key Lab Incubation Base of Xinjiang Major Diseases Research (2010DS890294) and Xinjiang Key Laboratory of Echinococcosis, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
Bruno GottsteinInstitute of Parasitology, University of Bern, Bern, Switzerland.
University of Bern · CHUniversité de franche-comté · FRUniversity of Toronto · CAXinjiang Medical University · CNFirst Affiliated Hospital of Xinjiang Medical University · CNSpiez Laboratory · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe growth potential of the tumor-like Echinococcus multilocularis metacestode (causing alveolar echinococcosis, AE) is directly linked to the nature/function of the periparasitic host immune-mediated processes. We previously showed that Fibrinogen-like-protein 2 (FGL2), a novel CD4+CD25+ Treg effector molecule, was over-expressed in the liver of mice experimentally infected with E. multilocularis. However, little is known about its contribution to the control of this chronic helminth infection. METHODS/

findingsKey parameters for infection outcome in E. multilocularis-infected fgl2-/- (AE-fgl2-/-) and wild type (AE-WT) mice at 1 and 4 month(s) post-infection were (i) parasite load (i. e. wet weight of parasitic metacestode tissue), and (ii) parasite cell proliferation as assessed by determining E. multilocularis 14-3-3 gene expression levels. Serum FGL2 levels were measured by ELISA. Spleen cells cultured with ConA for 48h or with E. multilocularis Vesicle Fluid (VF) for 96h were analyzed ex-vivo and in-vitro. In addition, spleen cells from non-infected WT mice were cultured with rFGL2/anti-FGL2 or rIL-17A/anti-IL-17A for further functional studies. For Treg-immune-suppression-assays, purified CD4+CD25+ Treg suspensions were incubated with CD4+ effector T cells in the presence of ConA and irradiated spleen cells as APCs. Flow cytometry and qRT-PCR were used to assess Treg, Th17-, Th1-, Th2-type immune responses and maturation of dendritic cells. We showed that AE-fgl2-/- mice exhibited (as compared to AE-WT-animals) (a) a significantly lower parasite load with reduced proliferation activity, (b) an increased T cell proliferative response to ConA, (c) reduced Treg numbers and function, and (d) a persistent capacity of Th1 polarization and DC maturation.

conclusionsFGL2 appears as one of the key players in immune regulatory processes favoring metacestode survival by promoting Treg cell activity and IL-17A production that contributes to FGL2-regulation. Prospectively, targeting FGL2 could be an option to develop an immunotherapy against AE and other chronic parasitic diseases.

Indexed as

AnimalsCD4 AntigensConcanavalin ADendritic CellsEchinococcosisEchinococcosis, HepaticEchinococcus multilocularisFibrinogenFlow CytometryInterleukin-17MiceTh17 CellsTh1 CellsTh2 CellsT-Lymphocytes, RegulatoryCD4 AntigensConcanavalin AFgl2 protein, mouseFibrinogenInterleukin-17

Identifiers

PMID25955764
PMCPMC4425495
OpenAlexW1525694679

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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.