title: Binding ofCandida albicansto Human CEACAM1 and CEACAM6 Modulates the Inflammatory Response of Intestinal Epithelial Cells.
abstract: Candida albicanscolonizes human mucosa, including the gastrointestinal tract, as a commensal. In immunocompromised patients,C. albicanscan 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. albicanscaused 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 toC. albicansIn CEACAM1-competent cells, the addition of recombinant soluble CEACAM6 reduced theC. albicans-induced CXCL8 secretion.IMPORTANCEThe 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 humansCandida albicanswith 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.
authors.affiliation: Septomics Research Center, Jena University Hospital, Jena, Germany.|Center for Sepsis Control and Care (CSCC), University Hospital Jena, Jena, Germany.
authors.forename: Esther
authors.identifier: 0000-0001-7389-6862
authors.initials: E
authors.lastname: Klaile
authors.affiliation: Septomics Research Center, Jena University Hospital, Jena, Germany.|Center for Sepsis Control and Care (CSCC), University Hospital Jena, Jena, Germany.
authors.forename: Mario M
authors.initials: MM
authors.lastname: Müller
authors.affiliation: Septomics Research Center, Jena University Hospital, Jena, Germany.
authors.forename: Miriam R
authors.initials: MR
authors.lastname: Schäfer
authors.affiliation: Septomics Research Center, Jena University Hospital, Jena, Germany.
authors.forename: Ann-Katrin
authors.initials: AK
authors.lastname: Clauder
authors.affiliation: Septomics Research Center, Jena University Hospital, Jena, Germany.
authors.forename: Sabina
authors.initials: S
authors.lastname: Feer
authors.affiliation: Septomics Research Center, Jena University Hospital, Jena, Germany.
authors.forename: Kerstin A
authors.initials: KA
authors.lastname: Heyl
authors.affiliation: Septomics Research Center, Jena University Hospital, Jena, Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Stock
authors.affiliation: Septomics Research Center, Jena University Hospital, Jena, Germany.
authors.forename: Tilman E
authors.initials: TE
authors.lastname: Klassert
authors.affiliation: Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany.|Faculty of Biology and Pharmacy, Infection Biology, Friedrich Schiller University, Jena, Germany.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Zipfel
authors.affiliation: Institute of Anatomy, Medical Faculty, University Duisburg-Essen, Essen, Germany.
authors.forename: Bernhard B
authors.initials: BB
authors.lastname: Singer
authors.affiliation: Septomics Research Center, Jena University Hospital, Jena, Germany hortense.slevogt@med.uni-jena.de.
authors.forename: Hortense
authors.initials: H
authors.lastname: Slevogt
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D002176:Candida albicans / Q000276:immunology* / Q000502:physiology*; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000032:analysis*; D011485:Protein Binding
chemical_list: D015703:Antigens, CD; C069847:CD66 antigens; C075729:CEACAM3 protein, human; C527875:CEACAM5 protein, human; C504117:CEACAM6 protein, human; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D007155:Immunologic Factors
keywords: C2BBe1; CEA; CEACAM1; CEACAM3; CEACAM5; CEACAM6; Candida albicans; Candida glabrata; carcinoembryonic antigen-related cell adhesion molecule; epithelial cells; innate immunity