Project A5

The role of CEACAM receptors for the recognition of Candida albicans and Aspergillus fumigatus

The immune responses induced by A. fumigatus and C. albicans infections are orchestrated by the recognition by and the interplay between diverse classes of receptors expressed in epithelial and immune cells. Recently, we identified members of the carcinoembryonic antigen (CEA)-related cell adhesion molecules (CEACAM) family as receptors for A. fumigatus und C. albicans. CEACAM receptors belong to the immunoglobulin (Ig) superfamily, containing an Ig variable region-like N-terminal domain followed by a varying number of Ig constant region-like domains exposed at the cell surface. Epithelially expressed CEACAMs are all presumed to facilitate bacterial colonization. Moreover, CEACAMs are expressed on several immune cells and their specific binding can influence immune cell activation. In the next funding period, we will characterize and analyze the impact of the CEACAM receptor family on the regulation for Candida- and Aspergillus-mediated immune responses. We will identify CEACAM-binding fungal surface molecules in C. albicans and A. fumigatus. To study the CEACAM - fungal interactions in host cells, individual CEACAM receptors will be examined for differences in eliciting responses to C. albicans and A. fumigatus. The biological relevance of the effect of human CEACAM receptors on the immune response to C. albicans and A. fumigatus will be studied in murine infection models. In summary, we will elucidate the impact of this family of receptors as possible fungal pattern recognition receptors for C. albicans and A. fumigatus.

The human CEACAM receptor family. Schematic depiction of important members of the human carcinoembryonic antigen-related cell adhesion molecules.
The human CEACAM receptor family. Schematic depiction of important members of the human carcinoembryonic antigen-related cell adhesion molecules.
Principal Investigator
Prof. Dr. Hortense Slevogt
Prof. Dr. Hortense Slevogt

Center for Innovation Competence (ZIK) Septomics  
Research group Fungal Septomics 

University Hospital Jena

Author Year Title Journal Links
Riebold, D.; Mahnkopf, M.; Wicht, K.; Zubiria-Barrera, C.; Heise, J.; Frank, M.; Misch, D.; Bauer, T.; Stocker, H.; Slevogt, H 2023 Axenic Long-Term Cultivation of Pneumocystis jirovecii. J. Fungi 9, 903 J. Fungi
Klassert TE, Hölzer M, Zubiria-Barrera C, Bethge J, Klaile E, Müller MM, Marz M, Slevogt H.  J Fungi (Basel). 2023 Oct 14;9(10):1014. doi: 10.3390/jof9101014. PMID: 37888270; PMCID: PMC10607568. 2023 Differential Transcriptional Responses of Human Granulocytes to Fungal Infection with Candida albicans and Aspergillus fumigatus. J Fungi 9(10):1014 PubMed
Klaile E, Prada Salcedo JP, Klassert TE, Besemer M, Bothe AK, Durotin A, Müller MM, Schmitt V, Luther CH, Dittrich M, Singer BB, Dandekar T, Slevogt H 2022 Antibody ligation of CEACAM1, CEACAM3, and CEACAM6, differentially enhance the cytokine release of human neutrophils in responses to Candida albicans. Cell Immunol 371: 104459 PubMed
Böttcher K, Braunschmidt K, Hirth G, Schärich K, Klassert TE, Stock M, Sorgatz J, Fischer-Burkart S, Ullrich S, Frankenberger S, Kritsch D, Kosan C, Küppers R, Strobl LJ, Slevogt H, Zimber-Strobl U, Jungnickel B 2021 Context-dependent regulation of immunoglobulin mutagenesis by p53. Molecular Immunology 138: 128–136 PubMed
Riebold D, Lubig J, Wolf P, Wolf C, Russow K, Loebermann M, Slevogt H, Mohr E, Feldhusen F, Reisinger EC 2020 First molecular detection of Pneumocystis spp. in red foxes (Vulpes vulpeslinnaeus, 1758) and raccoon dogs (Nyctereutes procyonoidesgray, 1834). Comp Immunol Microbiol Infect Dis 73: 101531 PubMed
Machata S, Müller MM, Lehmann R, Sieber S, Panagiotou G, Carvalho A, Cunha C, Lagrou K, Maertens J, Slevogt H, Jacobsen ID 2020 Proteome analysis of bronchoalveolar lavage fluids reveals host and fungal proteins highly expressed during invasive pulmonary aspergillosis in mice and humans. Virulence 11: 1337-51 Virulence
Cho S, Rudloff I, Lao J, Pang M, Goldberg R, Bui C, McLean C, Stock M, Klassert TE, Slevogt H, Mangan N, Cheng W, Fischer D, Gfröerer S, Sandhu M, Ngo D, Bujotzek A, Lariviere L, Schumacher F, Tiefenthaler G, Beker F, Collins C, Kamlin O, König K, Malhotra A, Tan K, Theda C, Veldman A, Ellisdon A, Whisstock J, Berger P, Nold-Petry C, Nold M 2020 Characterization of the pathoimmunology of necrotizing enterocolitis reveals novel therapeutic opportunities. Nat Commun 11: 5794 PubMed
Mirhakkak MH, Schäuble S, Klassert TE, Brunke S, Brandt P, Loos D, Uribe RV, Senne de Oliveira Lino F, Ni Y, Vylkova S, Slevogt H, Hube B, Weiss GJ, Sommer MOA, Panagiotou G 2020 Metabolic modeling predicts specific gut bacteria as key determinants for Candida albicans colonization levels. ISME J 15: 1257-70 PubMed
Töpfer N, Müller MM, Dahms M, Ramoji A, Popp J, Slevogt H, Neugebauer U 2019 Raman spectroscopy reveals LPS-induced changes of biomolecular composition in monocytic THP-1 cells in a label-free manner. Integr Biol (Camb) zyz009 PubMed
Klaile E, Müller MM, Brehme S, Zubiria-Barrera C, Klassert TE, Stock M, Durotin A, Nguyen TD, Feer S, Singer BB, Zipfel PF, Rudolphi S, Jacobsen ID, Slevogt H 2019 Unaltered fungal burden and lethality in human CEACAM1-transgenic mice during Candida albicans dissemination and systemic infection. Front Microbiol 10: 2703 PubMed
Lehmann R, Müller MM, Klassert TE, Driesch D, Stock M, Conrad T, Moore C, Schier U, Guthke R, Slevogt H 2018 Differential regulation of the transcriptomic and secretomic landscape of sensor and effector functions of human airway epithelial cells. Mucosal Immonol 11: 627-42 PubMed
Irmscher S, Döring N, Halder LD, Jo EAH, Kopka I, Dunker C, Jacobsen ID, Luo S, Slevogt H, Lorkowski S, Beyersdorf N, Zipfel PF, Skerka C 2018 Kallikrein cleaves C3 and activates complement. J Innate Immun 10: 94-105 PubMed
Goyal S, Castrillón Betancur JC, Klaile E, Slevogt H 2018 The Interaction of human pathogenic fungi with C-type Lectin receptors. Front Immunol 9: 1261 PubMed
Müller MM, Lehmann R, Klassert TE, Reifenstein S, Conrad T, Moore C, Kuhn A, Behnert A, Guthke R, Driesch D, Slevogt H 2017 Global analysis of glycoproteins identifies markers of endotoxin tolerant monocytes and GPR84 as a modulator of TNFα expression. Sci Rep 7: 838 PubMed
Klassert TE, Bräuer J, Hölzer M, Stock M, Riege K, Zubiría-Barrera C, Müller MM, Rummler S, Skerka C, Marz M, Slevogt H 2017 Differential effects of vitamins A and D on the transcriptional landscape of human monocytes during infection. Sci Rep 7: 40599 PubMed
Riege K, Hölzer M, Klassert TE, Barth E, Bräuer J, Collatz M, Hufsky F, Mostajo N, Stock M, Vogel B, Slevogt H, Marz M 2017 Massive effect on LncRNAs in human monocytes during fungal and bacterial infections and in response to vitamins A and D. Sci Rep 7: 40598 PubMed
Klaile E, Müller M, Schäfer MR, Feer S, Heyl K, Stock M, Klassert T, Zipfel P, Singer P 2017 Binding of Candida albicans to human CEACAM1 and CEACAM6 modulates the inflammatory response of intestinal epithelial cells. mBio 8: e02142-16 PubMed
Saraiva JP, Oswald M, Biering A, Röll D, Assmann C, Klassert T, Blaess M, Czakai K, Claus R, Löffler J, Slevogt H, König R 2017 Fungal biomarker discovery by integration of classifiers. BMC Genomics 18: 601 PubMed
Heinrich A, Heyl KA, Klaile E, Müller MM, Klassert TE, Wiessner A, Fischer K, Schumann RR, Seifert U, Riesbeck K, Moter A, Singer BB, Bachmann S, Slevogt H 2016 Moraxella catarrhalis induces CEACAM3-Syk-Card9-dependent activation of human granulocytes. Cell Microbiol 18: 1570-82 PubMed
Javaheri A, Kruse T, Moonens K, Mejías-Luque R, Debraekeleer A, Asche CI, Tegtmeyer N, Kalali B, Bach NC, Sieber SA, Hill DJ, Königer V, Hauck CR, Moskalenko R, Haas R, Busch DH, Klaile E, Slevogt H, Schmidt A, Backert S, Remaut H, Singer BB, Gerhard M 2016 Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs. Nat Microbiol 2: 16189 PubMed
Acosta-Herrera M, Lorenzo-Diaz F, Pino-Yanes M, Corrales A, Valladares F, Klassert TE, Valladares B, Slevogt H, Ma SF, Villar J, Flores C 2015 Lung transcriptomics during protective ventilatory support in sepsis-induced acute lung injury. PLoS One 10: e0132296 PubMed
Heyl KA, Klassert TE, Heinrich A, Müller MM, Klaile E, Dienemann H, Grünewald C, Bals R, Singer BB, Slevogt H 2014 Dectin-1 is expressed in human lung and mediates the pro-inflammatory immune response to non-typeable Haemophilus influenzae. mBio 5: e01492-14 PubMed
Klassert TE, Hanisch A, Bräuer J, Klaile E, Heyl KA, Mansour MM, Tam JM, Vyas JM, Slevogt H 2014 Modulatory role of vitamin A on the Candida albicans-induced immune response in human monocytes. Med Microbiol Immunol 203: 415-24 PubMed