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Pathways Regulating Cytosolic Phospholipase A(2) Activation and Eicosanoid Production in Macrophages by Candida albicans

Resident tissue macrophages are activated by the fungal pathogen Candida albicans to release eicosanoids, which are important modulators of inflammation and immune responses. Our objective was to identify the macrophage receptors engaged by C. albicans that mediate activation of group IVA cytosolic...

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Autores principales: Suram, Saritha, Gangelhoff, Todd A., Taylor, Philip R., Rosas, Marcela, Brown, Gordon D., Bonventre, Joseph V., Akira, Shizuo, Uematsu, Satoshi, Williams, David L., Murphy, Robert C., Leslie, Christina C.
Formato: Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945562/
https://www.ncbi.nlm.nih.gov/pubmed/20643646
http://dx.doi.org/10.1074/jbc.M110.143800
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author Suram, Saritha
Gangelhoff, Todd A.
Taylor, Philip R.
Rosas, Marcela
Brown, Gordon D.
Bonventre, Joseph V.
Akira, Shizuo
Uematsu, Satoshi
Williams, David L.
Murphy, Robert C.
Leslie, Christina C.
author_facet Suram, Saritha
Gangelhoff, Todd A.
Taylor, Philip R.
Rosas, Marcela
Brown, Gordon D.
Bonventre, Joseph V.
Akira, Shizuo
Uematsu, Satoshi
Williams, David L.
Murphy, Robert C.
Leslie, Christina C.
author_sort Suram, Saritha
collection PubMed
description Resident tissue macrophages are activated by the fungal pathogen Candida albicans to release eicosanoids, which are important modulators of inflammation and immune responses. Our objective was to identify the macrophage receptors engaged by C. albicans that mediate activation of group IVA cytosolic phospholipase A(2) (cPLA(2)α), a regulatory enzyme that releases arachidonic acid (AA) for production of prostaglandins and leukotrienes. A comparison of peritoneal macrophages from wild type and knock-out mice demonstrates that the β-glucan receptor Dectin-1 and MyD88 regulate early release of AA and eicosanoids in response to C. albicans. However, cyclooxygenase 2 (COX2) expression and later phase eicosanoid production are defective in MyD88(−/−) but not Dectin-1(−/−) macrophages. Furthermore, C. albicans-stimulated activation of MAPK and phosphorylation of cPLA(2)α on Ser-505 are regulated by MyD88 and not Dectin-1. In contrast, Dectin-1 mediates MAPK activation, cPLA(2)α phosphorylation, and COX2 expression in response to particulate β-glucan suggesting that other receptors engaged by C. albicans preferentially mediate these responses. Results also implicate the mannan-binding receptor Dectin-2 in regulating cPLA(2)α. C. albicans-stimulated MAPK activation and AA release are blocked by d-mannose and Dectin-2-specific antibody, and overexpression of Dectin-2 in RAW264.7 macrophages enhances C. albicans-stimulated MAPK activation, AA release, and COX2 expression. In addition, calcium mobilization is enhanced in RAW264.7 macrophages overexpressing Dectin-1 or -2. The results demonstrate that C. albicans engages both β-glucan and mannan-binding receptors on macrophages that act with MyD88 to regulate the activation of cPLA(2)α and eicosanoid production.
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spelling pubmed-29455622010-10-04 Pathways Regulating Cytosolic Phospholipase A(2) Activation and Eicosanoid Production in Macrophages by Candida albicans Suram, Saritha Gangelhoff, Todd A. Taylor, Philip R. Rosas, Marcela Brown, Gordon D. Bonventre, Joseph V. Akira, Shizuo Uematsu, Satoshi Williams, David L. Murphy, Robert C. Leslie, Christina C. J Biol Chem Cell Biology Resident tissue macrophages are activated by the fungal pathogen Candida albicans to release eicosanoids, which are important modulators of inflammation and immune responses. Our objective was to identify the macrophage receptors engaged by C. albicans that mediate activation of group IVA cytosolic phospholipase A(2) (cPLA(2)α), a regulatory enzyme that releases arachidonic acid (AA) for production of prostaglandins and leukotrienes. A comparison of peritoneal macrophages from wild type and knock-out mice demonstrates that the β-glucan receptor Dectin-1 and MyD88 regulate early release of AA and eicosanoids in response to C. albicans. However, cyclooxygenase 2 (COX2) expression and later phase eicosanoid production are defective in MyD88(−/−) but not Dectin-1(−/−) macrophages. Furthermore, C. albicans-stimulated activation of MAPK and phosphorylation of cPLA(2)α on Ser-505 are regulated by MyD88 and not Dectin-1. In contrast, Dectin-1 mediates MAPK activation, cPLA(2)α phosphorylation, and COX2 expression in response to particulate β-glucan suggesting that other receptors engaged by C. albicans preferentially mediate these responses. Results also implicate the mannan-binding receptor Dectin-2 in regulating cPLA(2)α. C. albicans-stimulated MAPK activation and AA release are blocked by d-mannose and Dectin-2-specific antibody, and overexpression of Dectin-2 in RAW264.7 macrophages enhances C. albicans-stimulated MAPK activation, AA release, and COX2 expression. In addition, calcium mobilization is enhanced in RAW264.7 macrophages overexpressing Dectin-1 or -2. The results demonstrate that C. albicans engages both β-glucan and mannan-binding receptors on macrophages that act with MyD88 to regulate the activation of cPLA(2)α and eicosanoid production. American Society for Biochemistry and Molecular Biology 2010-10-01 2010-07-18 /pmc/articles/PMC2945562/ /pubmed/20643646 http://dx.doi.org/10.1074/jbc.M110.143800 Text en © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version full access. Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) applies to Author Choice Articles
spellingShingle Cell Biology
Suram, Saritha
Gangelhoff, Todd A.
Taylor, Philip R.
Rosas, Marcela
Brown, Gordon D.
Bonventre, Joseph V.
Akira, Shizuo
Uematsu, Satoshi
Williams, David L.
Murphy, Robert C.
Leslie, Christina C.
Pathways Regulating Cytosolic Phospholipase A(2) Activation and Eicosanoid Production in Macrophages by Candida albicans
title Pathways Regulating Cytosolic Phospholipase A(2) Activation and Eicosanoid Production in Macrophages by Candida albicans
title_full Pathways Regulating Cytosolic Phospholipase A(2) Activation and Eicosanoid Production in Macrophages by Candida albicans
title_fullStr Pathways Regulating Cytosolic Phospholipase A(2) Activation and Eicosanoid Production in Macrophages by Candida albicans
title_full_unstemmed Pathways Regulating Cytosolic Phospholipase A(2) Activation and Eicosanoid Production in Macrophages by Candida albicans
title_short Pathways Regulating Cytosolic Phospholipase A(2) Activation and Eicosanoid Production in Macrophages by Candida albicans
title_sort pathways regulating cytosolic phospholipase a(2) activation and eicosanoid production in macrophages by candida albicans
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945562/
https://www.ncbi.nlm.nih.gov/pubmed/20643646
http://dx.doi.org/10.1074/jbc.M110.143800
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