Evidence map›Paper›PMID 41068074›Full record

ArticleNature communications2025

Brain-infiltrating CD4 T cells drive inflammatory microglia proliferation during cryptococcal meningitis in mice.

Sofia Hain, Man Shun Fu, Lucy Wigg, Lorna George, David Lecky, Alexander J Whitehead, Erin Clipston, Ko Sato, Masahiro Ono, Marcel Wuthrich and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 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. Review
  3. Fungal Infections in Disorders of Inborn Errors of Immunity.Clinical reviews in allergy & immunology · 2026
    Review
  4. 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

15 authors.

Sofia Hain *Institute of Immunology & Immunotherapy, University of Birmingham, Birmingham, UK.ORCID http://orcid.org/0000-0001-7993-2828
Man Shun Fu *Institute of Immunology & Immunotherapy, University of Birmingham, Birmingham, UK.
Lucy WiggInstitute of Microbiology & Infection, University of Birmingham, Birmingham, UK.
Lorna GeorgeInstitute of Immunology & Immunotherapy, University of Birmingham, Birmingham, UK.
David LeckyInstitute of Immunology & Immunotherapy, University of Birmingham, Birmingham, UK.
Alexander J WhiteheadDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
Erin ClipstonInstitute of Microbiology & Infection, University of Birmingham, Birmingham, UK.
Ko SatoDepartment of Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan.
Masahiro OnoDepartment of Life Sciences, Imperial College London, London, UK.ORCID http://orcid.org/0000-0002-9284-7326
Marcel WuthrichDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
Bruce KleinDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
Kazuyoshi KawakamiDepartment of Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan.
Julie RayesDepartment of Cardiovascular Sciences, College of Medicine and Health, School of Medical Sciences, University of Birmingham, Birmingham, UK.ORCID http://orcid.org/0000-0003-0499-6880
David BendingInstitute of Immunology & Immunotherapy, University of Birmingham, Birmingham, UK.ORCID http://orcid.org/0000-0003-0071-1163
Rebecca A DrummondInstitute of Immunology & Immunotherapy, University of Birmingham, Birmingham, UK. r.drummond@bham.ac.uk.ORCID http://orcid.org/0000-0001-5424-7074

Funding

Academy of Medical Sciences SBF004_1008RCUK | Medical Research Council (MRC) MR/S024611Wellcome Trust
6 · The paper itself

Abstract

Cryptococcal meningitis is a fungal infection in patients with compromised CD4 T cell function. CD4 T cells provide killing signals to macrophages, principally IFNγ, to limit intracellular fungal replication. However, CD4 T cells may also drive inflammatory tissue damage. Yet, it is not fully understood how fungal-specific CD4 T cells infiltrate the brain and how they influence functional phenotypes of CNS-resident myeloid cells. In the current work, we develop a mouse model to track fungal-specific CD4 T cells and determine their influence on microglia. We found IFNγ+ fungal-specific CD4 T cells have limited TCR signalling and characterise a population of inflammatory microglia that upregulate MHCII and IFNγ-regulated genes during infection. Inflammatory microglia have poor fungicidal capacity and significantly expand during infection, a process that depends on CD4 T cell infiltration. Taken together, these data identify the early inflammatory consequences of fungal-specific CD4 T cell infiltration and identify proliferating microglia as important drivers of brain inflammation during infection.

Indexed as

BrainCD4-Positive T-LymphocytesMeningitis, CryptococcalMicrogliaAnimalsCell ProliferationCryptococcus neoformansDisease Models, AnimalFemaleInflammationInterferon-gammaMacrophagesMaleMiceMice, Inbred C57BLInterferon-gamma

Identifiers

PMID41068074
PMCPMC12511619

What OpenQuestion holds

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LicenceCC BY
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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.