The Candida glabrata adhesin Epa1p causes adhesion, phagocytosis, and cytokine secretion by innate immune cells
Open accessAbstract
While Candida albicans is the most significant fungal pathogen for humans, Candida glabrata accounts for an increasing number of infections. Little is known about how C. glabrata interacts with the innate immune system, the first line of defense against such organisms. The C. glabrata adhesin Epa1p was previously shown to bind mammalian epithelial cells. We hypothesized that Epa1p mediates unique, nonopsonic binding to macrophages, leading to induction of immune responses. We found that Epa1p mediated adhesion by both C. glabrata (Cg) and transformed Saccharomyces cerevisiae (Sc(EPA1) ) to human macrophage-like cells, including Thp1 and U937 lines, and donor PBMCs. Adhesion was distinct from described mechanisms such as Dectin-1. Epa1p expression was necessary and sufficient for S. cerevisiae binding and phagocytosis, the latter of which was actin-mediated. Sc(EPA1) induced inflammatory cytokine production (IL-8 and TNF-α) by human PBMC-derived macrophages. Despite expressing Epa1p and binding to macrophages, Cg avoided phagocytosis and cytokine induction. In contrast to human results, in murine cell models (RAW264.7, J774A.1, and C57BL/6-derived cells), Epa1p-mediated binding was only revealed after blocking the Dectin-1 system. Recognition of Epa1p represents a novel mechanism by which human innate immune cells bind fungi, and for Sc(EPA1) results in phagocytosis and subsequent cytokine production.
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Epa1 is a calcium-dependent lectin that aids adhesion to epithelial cells and macrophages.
“The founding member of the Epa adhesin family, Epa1, is a calcium-dependent lectin, and aids adhesion to epithelial cells [32] and macrophages [33].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [33]
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- Authors
- Kuhn, D. M., & Vyas, V. K.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- Corresponding author
- Kuhn, Duncan M.
- Venue
- FEMS Yeast Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-01-23
- Volume
- 12
- Issue
- 4
- Pages
- 398-414
- ISSN
- 1567-1356 (ISSN-L)
- OpenAlex
- W1986702564
- Cited by
- 38
- References
- 82
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 3 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 4 · 2016: 7 · 2015: 4 · 2014: 2 · 2013: 4 · 2012: 1
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEMS Yeast Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5t32hl007874-15, 5k08ai071023-03)
- Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology
- National Heart, Lung, and Blood Institute (HL-07874)
- National Institute of Allergy and Infectious Diseases (AI729353, AI071023-01A1)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Keywords
- Candida glabrata, fungal adhesins, macrophage adhesion, phagocytosis, innate immune response, cytokine production, interleukin-8, TNF-α, Dectin-1, host-pathogen interaction, fungal virulence
- MeSH terms
- Animals, Cell Adhesion, Cells, Cultured, Fungal Proteins, Humans, Macrophages, Phagocytosis, Saccharomyces cerevisiae, Transformation, Genetic, Gene Expression, Cytokines, Lectins, Candida glabrata, Mice
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