Serum amyloid P component binds fungal surface amyloid and decreases human macrophage phagocytosis and secretion of inflammatory cytokines

Nicole E. Behrens, Peter N. Lipke, Darrell Pilling, Richard H. Gomer, Stephen A. Klotz

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

In 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 al-bicans dampens the innate immune response to this fungus. Many pathogenic fungi have cell surface amyloid-like structures important for adhesion and biofilm forma-tion. 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 potenti-ated 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-β), 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 re-sponsible for recognizing invading microbes, ingesting them, and sending appropri-ate signals to other immune cells. We have found that human macrophages can rec-ognize 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 sel-dom 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.

Original languageEnglish (US)
Article numbere00218-19
Pages (from-to)1-14
Number of pages14
JournalmBio
Volume10
Issue number2
DOIs
StatePublished - 2019

Keywords

  • Cytokines
  • Functional amyloid
  • Innate immunity
  • Macrophage polarization
  • SAP

ASJC Scopus subject areas

  • Microbiology
  • Virology

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