Project A5

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

Project Description

The Dectin-1-dependent immune response is an important characteristic of infections with Candida albicans and Aspergillus fumigatus. Candida spp. as well as Aspergillus spp. infections often occur in immunocompromised hosts and as emerging problem resulting from medical intervention including long term glucocorticoid therapy. The biological activities of glucocorticoids are mediated through the intracellular glucocorticoid receptor (GR), which belongs to the nuclear receptor (NR) subfamily. Little is known about the molecular determinants of the cross-talk between nuclear receptors and the Dectin-1 receptor-dependent immune responses. We hypothesise that the molecular cross-talk between several members of the NRs and Dectin-1 is of particular importance for the fine-tuning of the C. albicans and A. fumigatus induced immune activation in granulocytes, monocytes and dendritic cells. In this proposed project, we will characterise the functional role of the interaction of Dectin-1 with its agonist β-glucan for the orchestration of the immune responses in these cells types by making use of whole transcriptome analysis. Furthermore in a comprehensive study we will identify the specific function of Dectin-1 in C. albicans and A. fumigatus induced cell activation by combining Dectin-1 gene knock-down (siRNA) and receptor blocking. In a next step, we aim to investigate the functional cross-talk between Dectin-1 and specific agonists of NRs to study the transcriptional mechanisms of NR-dependent modulations of the Dectin-1 specific immune responses. The characterisation of the role of Dectin-1 and NRs for fungal detection and pattern recognition receptor (PRR)-mediated immune responses are likely to contribute to a better understanding of disease mechanisms, potentially leading to new strategies for the development of therapeutic approaches in fungal infections.

Principal Investigator

Prof. Dr. Hortense Slevogt
Prof. Dr. Hortense Slevogt

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

University Hospital Jena

hortense.slevogt@med.uni-jena.de

Publications

Author Year Title Journal Links
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
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
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
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
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(2) pii: 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