Binding of <italic toggle="yes">Candida albicans</italic> to Human CEACAM1 and CEACAM6 Modulates the Inflammatory Response of Intestinal Epithelial Cells

ABSTRACT Candida albicans colonizes human mucosa, including the gastrointestinal tract, as a commensal. In immunocompromised patients, C. albicans can breach the intestinal epithelial barrier and cause fatal invasive infections. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1; CD6...

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Autores principales:	Esther Klaile, Mario M. Müller, Miriam R. Schäfer, Ann-Katrin Clauder, Sabina Feer, Kerstin A. Heyl, Magdalena Stock, Tilman E. Klassert, Peter F. Zipfel, Bernhard B. Singer, Hortense Slevogt
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	C2BBe1 CEA CEACAM1 CEACAM3 CEACAM5 CEACAM6 Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2dd2fae738ff40289e02301da37c6756
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spelling	oai:doaj.org-article:2dd2fae738ff40289e02301da37c67562021-11-15T15:51:00ZBinding of <italic toggle="yes">Candida albicans</italic> to Human CEACAM1 and CEACAM6 Modulates the Inflammatory Response of Intestinal Epithelial Cells10.1128/mBio.02142-162150-7511https://doaj.org/article/2dd2fae738ff40289e02301da37c67562017-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02142-16https://doaj.org/toc/2150-7511ABSTRACT Candida albicans colonizes human mucosa, including the gastrointestinal tract, as a commensal. In immunocompromised patients, C. albicans can breach the intestinal epithelial barrier and cause fatal invasive infections. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1; CD66a), CEACAM5 (CEA), and CEACAM6 (CD66c) are immunomodulatory receptors expressed on human mucosa and are recruited by bacterial and viral pathogens. Here we show for the first time that a fungal pathogen (i.e., C. albicans) also binds directly to the extracellular domain of human CEACAM1, CEACAM3, CEACAM5, and CEACAM6. Binding was specific for human CEACAMs and mediated by the N-terminal IgV-like domain. In enterocytic C2BBe1 cells, C. albicans caused a transient tyrosine phosphorylation of CEACAM1 and induced higher expression of membrane-bound CEACAM1 and soluble CEACAM6. Lack of the CEACAM1 receptor after short hairpin RNA (shRNA) knockdown abolished CXCL8 (interleukin-8) secretion by C2BBe1 cells in response to C. albicans. In CEACAM1-competent cells, the addition of recombinant soluble CEACAM6 reduced the C. albicans-induced CXCL8 secretion. IMPORTANCE The present study demonstrates for the first time that fungal pathogens can be recognized by at least four members of the immunomodulatory CEACAM receptor family: CEACAM1, -3, -5, and -6. Three of the four receptors (i.e., CEACAM1, -5, and -6) are expressed in mucosal cells of the intestinal tract, where they are implicated in immunomodulation and control of tissue homeostasis. Importantly, the interaction of the major fungal pathogen in humans Candida albicans with CEACAM1 and CEACAM6 resulted in an altered epithelial immune response. With respect to the broad impact of CEACAM receptors on various aspects of the innate and the adaptive immune responses, in particular epithelial, neutrophil, and T cell behavior, understanding the role of CEACAMs in the host response to fungal pathogens might help to improve management of superficial and systemic fungal infections.Esther KlaileMario M. MüllerMiriam R. SchäferAnn-Katrin ClauderSabina FeerKerstin A. HeylMagdalena StockTilman E. KlassertPeter F. ZipfelBernhard B. SingerHortense SlevogtAmerican Society for MicrobiologyarticleC2BBe1CEACEACAM1CEACAM3CEACAM5CEACAM6MicrobiologyQR1-502ENmBio, Vol 8, Iss 2 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	C2BBe1 CEA CEACAM1 CEACAM3 CEACAM5 CEACAM6 Microbiology QR1-502
spellingShingle	C2BBe1 CEA CEACAM1 CEACAM3 CEACAM5 CEACAM6 Microbiology QR1-502 Esther Klaile Mario M. Müller Miriam R. Schäfer Ann-Katrin Clauder Sabina Feer Kerstin A. Heyl Magdalena Stock Tilman E. Klassert Peter F. Zipfel Bernhard B. Singer Hortense Slevogt Binding of <italic toggle="yes">Candida albicans</italic> to Human CEACAM1 and CEACAM6 Modulates the Inflammatory Response of Intestinal Epithelial Cells
description	ABSTRACT Candida albicans colonizes human mucosa, including the gastrointestinal tract, as a commensal. In immunocompromised patients, C. albicans can breach the intestinal epithelial barrier and cause fatal invasive infections. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1; CD66a), CEACAM5 (CEA), and CEACAM6 (CD66c) are immunomodulatory receptors expressed on human mucosa and are recruited by bacterial and viral pathogens. Here we show for the first time that a fungal pathogen (i.e., C. albicans) also binds directly to the extracellular domain of human CEACAM1, CEACAM3, CEACAM5, and CEACAM6. Binding was specific for human CEACAMs and mediated by the N-terminal IgV-like domain. In enterocytic C2BBe1 cells, C. albicans caused a transient tyrosine phosphorylation of CEACAM1 and induced higher expression of membrane-bound CEACAM1 and soluble CEACAM6. Lack of the CEACAM1 receptor after short hairpin RNA (shRNA) knockdown abolished CXCL8 (interleukin-8) secretion by C2BBe1 cells in response to C. albicans. In CEACAM1-competent cells, the addition of recombinant soluble CEACAM6 reduced the C. albicans-induced CXCL8 secretion. IMPORTANCE The present study demonstrates for the first time that fungal pathogens can be recognized by at least four members of the immunomodulatory CEACAM receptor family: CEACAM1, -3, -5, and -6. Three of the four receptors (i.e., CEACAM1, -5, and -6) are expressed in mucosal cells of the intestinal tract, where they are implicated in immunomodulation and control of tissue homeostasis. Importantly, the interaction of the major fungal pathogen in humans Candida albicans with CEACAM1 and CEACAM6 resulted in an altered epithelial immune response. With respect to the broad impact of CEACAM receptors on various aspects of the innate and the adaptive immune responses, in particular epithelial, neutrophil, and T cell behavior, understanding the role of CEACAMs in the host response to fungal pathogens might help to improve management of superficial and systemic fungal infections.
format	article
author	Esther Klaile Mario M. Müller Miriam R. Schäfer Ann-Katrin Clauder Sabina Feer Kerstin A. Heyl Magdalena Stock Tilman E. Klassert Peter F. Zipfel Bernhard B. Singer Hortense Slevogt
author_facet	Esther Klaile Mario M. Müller Miriam R. Schäfer Ann-Katrin Clauder Sabina Feer Kerstin A. Heyl Magdalena Stock Tilman E. Klassert Peter F. Zipfel Bernhard B. Singer Hortense Slevogt
author_sort	Esther Klaile
title	Binding of <italic toggle="yes">Candida albicans</italic> to Human CEACAM1 and CEACAM6 Modulates the Inflammatory Response of Intestinal Epithelial Cells
title_short	Binding of <italic toggle="yes">Candida albicans</italic> to Human CEACAM1 and CEACAM6 Modulates the Inflammatory Response of Intestinal Epithelial Cells
title_full	Binding of <italic toggle="yes">Candida albicans</italic> to Human CEACAM1 and CEACAM6 Modulates the Inflammatory Response of Intestinal Epithelial Cells
title_fullStr	Binding of <italic toggle="yes">Candida albicans</italic> to Human CEACAM1 and CEACAM6 Modulates the Inflammatory Response of Intestinal Epithelial Cells
title_full_unstemmed	Binding of <italic toggle="yes">Candida albicans</italic> to Human CEACAM1 and CEACAM6 Modulates the Inflammatory Response of Intestinal Epithelial Cells
title_sort	binding of <italic toggle="yes">candida albicans</italic> to human ceacam1 and ceacam6 modulates the inflammatory response of intestinal epithelial cells
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/2dd2fae738ff40289e02301da37c6756
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Binding of <italic toggle="yes">Candida albicans</italic> to Human CEACAM1 and CEACAM6 Modulates the Inflammatory Response of Intestinal Epithelial Cells

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