Evidence map›Paper›PMID 29782541›Full record

ArticlePLoS pathogens2018

An unappreciated role for neutrophil-DC hybrids in immunity to invasive fungal infections.

J Scott Fites, Michael Gui, John F Kernien, Paige Negoro, Zeina Dagher, David B Sykes, Jeniel E Nett, Michael K Mansour, Bruce S Klein

Abstract read
In one paragraph

Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
–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

46 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
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  6. Article
  7. Article
  8. IL-21-dependent Ly6CCell death discovery · 2025
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  15. Review
  16. Human CD79bFrontiers in immunology · 2023
    Article
  17. Article
  18. Quo Vadis? Immunodynamics of Myeloid Cells after Myocardial Infarction.International journal of molecular sciences · 2022
    Review
  19. Article
  20. 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

9 authors.

J Scott FitesDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.ORCID 0000-0003-4294-730X
Michael GuiDepartment of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.ORCID 0000-0002-7385-8783
John F KernienDepartment of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.ORCID 0000-0002-4424-7713
Paige NegoroDivision of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Zeina DagherDivision of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
David B SykesCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.ORCID 0000-0002-9788-0221
Jeniel E NettDepartment of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.ORCID 0000-0001-8587-6244
Michael K MansourDivision of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.ORCID 0000-0001-8892-8695
Bruce S KleinDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.ORCID 0000-0003-3212-1539

Funding

PROTECTIVE IMMUNE RESPONSES TO BLASTOMYCES DERMATITIDISR01AI040996 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI KLEIN, BRUCE STEVEN, WUETHRICH, MARCEL · 1997 to 2023
$10.4M
Molecular Pathogenesis of BlastomycosisR37AI035681 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI BRUCE Steven KLEIN · 2004 to 2026
$6.9M
Microbial Pathogenesis &Host Responses Training ProgramT32AI055397 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI KLEIN, BRUCE STEVEN · 2003 to 2024
$5.5M
Regulation of vaccine-induced anti-fungal Th17 cellsR01AI093553 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI WUETHRICH, MARCEL · 2011 to 2020
$4.5M
MOLECULAR PATHOGENESIS OF BLASTOMYCOSISR01AI035681 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI KLEIN, BRUCE STEVEN · 1995 to 2019
$3.9M
Lung epithelial cell regulation of immunity to inhaled fungiR01AI130411 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI KLEIN, BRUCE STEVEN · 2018 to 2021
$2.0M
Mechanisms of Candida Biofilm Immune EvasionK08AI108727 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI NETT, JENIEL E · 2014 to 2018
$960k
Subcellular Mechanisms for Fungal Phagosome Maturation in MacrophagesK08AI110655 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI MANSOUR, MICHAEL K · 2014 to 2017
$759k
NIAID NIH HHS K08 AI108727NIAID NIH HHS K08 AI110655NIAID NIH HHS R01 AI035681NIAID NIH HHS R01 AI040996NIAID NIH HHS R01 AI093553NIAID NIH HHS R01 AI130411NIAID NIH HHS R37 AI035681NIAID NIH HHS T32 AI055397NIH HHS K08 AI10655NIH HHS R01 AI035681NIH HHS R01 AI040996NIH HHS T32 AI055397
6 · The paper itself

Abstract

Neutrophils are classically defined as terminally differentiated, short-lived cells; however, neutrophils can be long-lived with phenotypic plasticity. During inflammation, a subset of neutrophils transdifferentiate into a population called neutrophil-DC hybrids (PMN-DCs) having properties of both neutrophils and dendritic cells. While these cells ubiquitously appear during inflammation, the role of PMN-DCs in disease remains poorly understood. We observed the differentiation of PMN-DCs in pre-clinical murine models of fungal infection: blastomycosis, aspergillosis and candidiasis. Using reporter strains of fungal viability, we found that PMN-DCs associate with fungal cells and kill them more efficiently than undifferentiated canonical neutrophils. During pulmonary blastomycosis, PMN-DCs comprised less than 1% of leukocytes yet contributed up to 15% of the fungal killing. PMN-DCs displayed higher expression of pattern recognition receptors, greater phagocytosis, and heightened production of reactive oxygen species compared to canonical neutrophils. PMN-DCs also displayed prominent NETosis. To further study PMN-DC function, we exploited a granulocyte/macrophage progenitor (GMP) cell line, generated PMN-DCs to over 90% purity, and used them for adoptive transfer and antigen presentation studies. Adoptively transferred PMN-DCs from the GMP line enhanced protection against systemic infection in vivo. PMN-DCs pulsed with antigen activated fungal calnexin-specific transgenic T cells in vitro and in vivo, promoting the production of interferon-γ and interleukin-17 in these CD4+ T cells. Through direct fungal killing and induction of adaptive immunity, PMN-DCs are potent effectors of antifungal immunity and thereby represent innovative cell therapeutic targets in treating life-threatening fungal infections.

Indexed as

Adoptive TransferAnimalsAntigen PresentationAspergillus fumigatusBlastomycesBlastomycosisBone Marrow CellsCandida albicansDendritic CellsFlow CytometryHybrid CellsInvasive Fungal InfectionsKidneyLungLung Diseases, FungalLymph NodesNitrous OxideReactive Oxygen Species

Identifiers

PMID29782541
PMCPMC5983859

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.