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.
Principal Investigator
Prof. Dr. Hortense Slevogt
Center for Innovation Competence (ZIK) Septomics
Research group Fungal Septomics
University Hospital Jena
Publications
| 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 |