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dc.contributor.authorBehrens, Nicole E
dc.contributor.authorLipke, Peter N
dc.contributor.authorPilling, Darrell
dc.contributor.authorGomer, Richard H
dc.contributor.authorKlotz, Stephen A
dc.date.accessioned2019-08-20T17:48:37Z
dc.date.available2019-08-20T17:48:37Z
dc.date.issued2019-03-12
dc.identifier.citationBehrens, N. E., Lipke, P. N., Pilling, D., Gomer, R. H., & Klotz, S. A. (2019). Serum Amyloid P Component Binds Fungal Surface Amyloid and Decreases Human Macrophage Phagocytosis and Secretion of Inflammatory Cytokines. mBio, 10(2), e00218-19.en_US
dc.identifier.issn2150-7511
dc.identifier.pmid30862745
dc.identifier.doi10.1128/mBio.00218-19
dc.identifier.urihttp://hdl.handle.net/10150/633890
dc.description.abstractIn patients with invasive fungal diseases, there is often little cellular inflammatory response. We tested the idea that binding of the human constitutive plasma protein serum amyloid P component (SAP) (also called PTX2) to Candida albicans dampens the innate immune response to this fungus. Many pathogenic fungi have cell surface amyloid-like structures important for adhesion and biofilm formation. Human SAP bound to fungi that expressed functional cell surface amyloid, but SAP had minimal binding to fungi with reduced expression of cell surface amyloid. In the absence of SAP, phagocytosis of fungi by human macrophages was potentiated by expression of amyloid on the fungi. SAP binding to fungi inhibited their phagocytosis by macrophages. Macrophages pretreated with SAP displayed reduced fungal phagocytosis, reduced secretion of inflammatory cytokines (IFN-γ, IL-6, and TNF-α), and increased secretion of the anti-inflammatory cytokine IL-10. SAP bound to fungi or added to the medium upregulated the expression of the anti-inflammatory receptor CD206 on macrophages. These findings suggest that SAP bound to amyloid-like structures on fungal cells dampens the host cellular immune response in fungal diseases such as invasive candidiasis.IMPORTANCE Macrophages are a key part of our innate immune system and are responsible for recognizing invading microbes, ingesting them, and sending appropriate signals to other immune cells. We have found that human macrophages can recognize invading yeast pathogens that have a specific molecular pattern of proteins on their surfaces: these proteins have structures similar to the structures of amyloid aggregates in neurodegenerative diseases like Alzheimer's disease. However, this surface pattern also causes the fungi to bind a serum protein called serum amyloid P component (SAP). In turn, the SAP-coated yeasts are poorly recognized and seldom ingested by the macrophages, and the macrophages have a more tolerant and less inflammatory response in the presence of SAP. Therefore, we find that surface structures on the yeast can alter how the macrophages react to invading microbes.en_US
dc.description.sponsorshipNIH [HL118507]en_US
dc.language.isoenen_US
dc.publisherAMER SOC MICROBIOLOGYen_US
dc.rightsCopyright © 2019 Behrens et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectSAPen_US
dc.subjectcytokinesen_US
dc.subjectfunctional amyloiden_US
dc.subjectinnate immunityen_US
dc.subjectmacrophage polarizationen_US
dc.titleSerum Amyloid P Component Binds Fungal Surface Amyloid and Decreases Human Macrophage Phagocytosis and Secretion of Inflammatory Cytokinesen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Dept Immunobiolen_US
dc.contributor.departmentUniv Arizona, Dept Meden_US
dc.identifier.journalMBIOen_US
dc.description.noteOpen access journalen_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
dc.source.journaltitlemBio
refterms.dateFOA2019-08-20T17:48:38Z


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Copyright © 2019 Behrens et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Except where otherwise noted, this item's license is described as Copyright © 2019 Behrens et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.