Evidence map›Paper›PMID 26582948›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2016

Zinc and Manganese Chelation by Neutrophil S100A8/A9 (Calprotectin) Limits Extracellular Aspergillus fumigatus Hyphal Growth and Corneal Infection.

Heather L Clark, Anupam Jhingran, Yan Sun, Chairut Vareechon, Steven de Jesus Carrion, Eric P Skaar, Walter J Chazin, José Antonio Calera, Tobias M Hohl, Eric Pearlman

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed
7.4field-weighted citation impact, top 2% 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

98 citing papers in PubMed, 148 citations in OpenAlex.

  1. Review
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  11. Metals at the Host-Fungal Pathogen Battleground.Annual review of microbiology · 2024
    Review
  12. Perforin-2 is dispensable for host defense againstbioRxiv : the preprint server for biology · 2024
    Article
  13. Article
  14. Review
  15. Article
  16. Article
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  18. Article
  19. Viral nanoparticle vaccines against S100A9 reduce lung tumor seeding and metastasis.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  20. Article

38 more citing papers are in PubMed but not listed here.

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

10 authors at 5 institutions in 2 countries.

Heather L ClarkDepartment of Ophthalmology and Visual Science, Case Western Reserve University, Cleveland, OH 44106; Department of Ophthalmology, University of California, Irvine, Irvine, CA 92697; Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697;
Anupam JhingranInfectious Disease Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065;
Yan SunDepartment of Ophthalmology and Visual Science, Case Western Reserve University, Cleveland, OH 44106;
Chairut VareechonDepartment of Ophthalmology and Visual Science, Case Western Reserve University, Cleveland, OH 44106;
Steven de Jesus CarrionDepartment of Ophthalmology and Visual Science, Case Western Reserve University, Cleveland, OH 44106;
Eric P SkaarDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232; Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN 37212;
Walter J ChazinDepartment of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232; Center for Structural Biology, Vanderbilt University School of Medicine, Nashville, TN 37232; and.
José Antonio CaleraInstituto de Biología Funcional y Genómica, Centro Mixto del Consejo Superior de Investigaciones Científicas y Universidad de Salamanca, 37002 Salamanca, Spain.
Tobias M HohlInfectious Disease Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065;
Eric PearlmanDepartment of Ophthalmology and Visual Science, Case Western Reserve University, Cleveland, OH 44106; Department of Ophthalmology, University of California, Irvine, Irvine, CA 92697; Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697; Eric.Pearlman@uci.edu.
Case Western Reserve University · USMemorial Sloan Kettering Cancer Center · USVanderbilt University · USUniversidad de Salamanca · ESUniversity of California, Irvine · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4M
TISSUE CULTURE AND HYBRIDOMA MODULEP30EY011373 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI Irina A Pikuleva · 1997 to 2026
$17.7M
Host-mediated zinc sequestration during Acinetobacter baumannii infectionR01AI101171 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WALTER J. CHAZIN, DAVID P. GIEDROC · 2013 to 2026
$8.2M
MOLECULAR BIOPHYSICS TRAINING PROGRAM AT VANDERBILTT32GM008320 · NIGMS · VANDERBILT UNIVERSITY · PI CHAZIN, WALTER J. · 1989 to 2023
$7.9M
Pathogenesis of Fungal KeratitisR01EY018612 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI PEARLMAN, ERIC · 2008 to 2022
$6.9M
VISUAL SCIENCES TRAINING PROGRAMT32EY007157 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI Johannes Friedrich von Lintig · 2000 to 2026
$5.5M
INITIATION OF THE IMMUNE RESPONSE TO ASPERGILLUS FUMIGATUSR01AI093808 · NIAID · SLOAN-KETTERING INST CAN RESEARCH · PI HOHL, TOBIAS M · 2011 to 2020
$4.9M
INITIATION OF THE IMMUNE RESPONSE TO ASPERGILLUS FUMIGATUSR37AI093808 · NIAID · SLOAN-KETTERING INST CAN RESEARCH · PI TOBIAS M HOHL · 2021 to 2026
$4.2M
Immunology Training Program-PredoctoralT32AI089474 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI COBB, BRIAN A · 2010 to 2025
$3.4M
Dissection of Macrophage Antifungal Activity against Aspergillus fumigatusR21AI105617 · NIAID · SLOAN-KETTERING INST CAN RESEARCH · PI HOHL, TOBIAS M · 2013 to 2014
$473k
Neutrophil calprotectin and neutrophil extracellular traps (NETs) in corneal defense and damage during fungal keratitis.F30EY025548 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI CLARK, HEATHER LYNN · 2015 to 2016
$97k
NCI NIH HHS P30 CA008748NEI NIH HHS 1F30EY025548-01NEI NIH HHS F30 EY025548NEI NIH HHS P30 EY011373NEI NIH HHS P30EY011373NEI NIH HHS R01 EY018612NEI NIH HHS R01 EY18612NEI NIH HHS T32 EY007157NIAID NIH HHS 5T32AI089474NIAID NIH HHS R01 AI093808NIAID NIH HHS R01 AI101171NIAID NIH HHS R21 AI105617NIAID NIH HHS R37 AI093808NIAID NIH HHS T32 AI089474NIGMS NIH HHS T32 GM007250NIGMS NIH HHS T32 GM008320
6 · The paper itself

Abstract

Calprotectin, a heterodimer of S100A8 and S100A9, is an abundant neutrophil protein that possesses antimicrobial activity primarily because of its ability to chelate zinc and manganese. In the current study, we showed that neutrophils from calprotectin-deficient S100A9(-/-) mice have an impaired ability to inhibit Aspergillus fumigatus hyphal growth in vitro and in infected corneas in a murine model of fungal keratitis; however, the ability to inhibit hyphal growth was restored in S100A9(-/-) mice by injecting recombinant calprotectin. Furthermore, using recombinant calprotectin with mutations in either the Zn and Mn binding sites or the Mn binding site alone, we show that both zinc and manganese binding are necessary for calprotectin's antihyphal activity. In contrast to hyphae, we found no role for neutrophil calprotectin in uptake or killing of intracellular A. fumigatus conidia either in vitro or in a murine model of pulmonary aspergillosis. We also found that an A. fumigatus ∆zafA mutant, which demonstrates deficient zinc transport, exhibits impaired growth in infected corneas and following incubation with neutrophils or calprotectin in vitro as compared with wild-type. Collectively, these studies demonstrate a novel stage-specific susceptibility of A. fumigatus to zinc and manganese chelation by neutrophil-derived calprotectin.

Indexed as

AdolescentAdultAgedAnimalsAspergillus fumigatusBiological TransportCalgranulin ACalgranulin BChelating AgentsCorneaDisease Models, AnimalHumansHyphaeKeratitisLeukocyte L1 Antigen ComplexManganeseCalgranulin ACalgranulin BChelating AgentsLeukocyte L1 Antigen ComplexManganeseS100a8 protein, mouseS100A9 protein, mouseZinc

Identifiers

PMID26582948
PMCPMC4684987
OpenAlexW2194700173

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.