| Metallomic analysis of macrophages infected with Histoplasma capsulatum reveals a fundamental role for zinc in host defenses. | |
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MedLine Citation:
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PMID: 20731582 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The fungal pathogen Histoplasma capsulatum evades the innate and adaptive immune responses and thrives within resting macrophages. Cytokines that induce antimicrobial activity, such as granulocyte macrophage colony-stimulating factor (GM-CSF), inhibit H. capsulatum growth in macrophages. Conversely, interleukin 4 inhibits the killing of intracellular pathogens. Using inductively coupled plasma mass spectrometry, we examined alterations in the metal homeostasis of murine H. capsulatum-infected macrophages that were exposed to activating cytokines. Decreases in the levels of iron (Fe(2+) and Fe(3+)) and zinc (Zn(2+)) were observed in infected, GM-CSF-treated macrophages compared with those in infected controls. Interleukin 4 reversed the antifungal activity of GM-CSF-activated macrophages and was associated with increased intracellular Zn(2+) levels. Chelation of Zn(2+) inhibited yeast replication in both the absence of macrophages and the presence of macrophages. Treatment of cells with GM-CSF altered the host Zn(2+) binding species profile. These results establish that Zn(2+) deprivation may be a host defense mechanism utilized by macrophages. |
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Authors:
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Michael S Winters; Qilin Chan; Joseph A Caruso; George S Deepe |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: The Journal of infectious diseases Volume: 202 ISSN: 1537-6613 ISO Abbreviation: J. Infect. Dis. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-08-31 Completed Date: 2010-09-22 Revised Date: 2012-05-07 |
Medline Journal Info:
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Nlm Unique ID: 0413675 Medline TA: J Infect Dis Country: United States |
Other Details:
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Languages: eng Pagination: 1136-45 Citation Subset: AIM; IM |
Affiliation:
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Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0560, USA. winterms@ucmail.uc.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Chelating Agents / metabolism Cytokines / immunology* Histoplasma / immunology* Iron / analysis, immunology Macrophages, Peritoneal / chemistry*, immunology*, microbiology Mass Spectrometry Mice Mice, Inbred C57BL Zinc / analysis*, immunology* |
| Grant Support | |
ID/Acronym/Agency:
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AI-73337/AI/NIAID NIH HHS; AI-83313/AI/NIAID NIH HHS; R01 AI073337-04/AI/NIAID NIH HHS; R01 AI083313-02/AI/NIAID NIH HHS; R01 AI083313-03/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chelating Agents; 0/Cytokines; 7439-89-6/Iron; 7440-66-6/Zinc |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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