Chronic inflammation negatively affects systemic anti-viral host defense and the clearance of bacterial and viral infections. In this project we aim to unravel the impact of chronic liver inflammation on the anti-viral immune responses using LCMV and influenza A virus (IAV) infection models.
Malaria infection is still a major cause of childhood mortatility, which underlines the medical need for a protective vaccine. Vaccination using large numbers of attenuated Sporozoites (SPZ) is in principle able to induce protective tissue resident memory T-cells (TRM) against liver stage malaria, but it is impractical for routine use. In this project we evaluate whether novel vaccine adjuvants that selectively engage nucleic acid sensors of the innate immune system improve the robustness and persistence of the TRM response, while allowing a dose sparing use of attenuated SPZ.
The chemokines CCL17 and CCL22 promote T cell/dendritic cell interactions during the induction of adaptive immune responses. CCL17 has been associated with the pathogenesis of allergic and inflammatory diseases, whereas CCL22 appears to rather play an immunosuppressive role. Using a mouse model for invasive Salmonellosis and specific knockout mice for both chemokines, we study the influence of CCL17 and CCL22 on the immune responses against Salmonella enterica serovar Typhimurium after oral infection. We are analyzing the myeloid cell populations responsible for transporting bacteria from the gut to mesenteric lymph nodes and investigate the importance of the chemokines for the induction of antigen-specific CD4 T cell responses in the context of vaccination. This analysis is further facilitated by the development of novel MHC class II tetramers for detection of Salmonella-specific T cells.
Legionella spp may cause a serious type of bacterial pneumonia called Legionnaire's disease and thus, pose a significant health risk in man. In collaboration with Prof. van Driel, University of Melbourne, we are investigating the cellular and molecular mechanisms governing host immune responses against Legionella. Using molecular, immunological, microbiological and imaging techniques, we are investigating (1) myeloid cells that are permissive for Legionella infection and replication; (2) the role of inflammasome activation in defence against Legionella by using genetically-modified mouse models and visualization of inflammasome activation, (3) molecular pathways in myeloid cells induced by Legionella infection, and (4) the contribution of lymphoid cells in the defence against Legionella. These studies will highlight key mechanisms controlling Legionella replication and may contribute towards new therapeutic strategies for pulmonary infections.
XCL1 is a chemokine that is expressed by NK cells and CD8 T cells upon activation. The receptor for XCL1 is called XCR1 and is exclusively expressed on a subset of Dendritic cells. In this project we address the role of the XCL1-XCR1 axis in the context of acute viral infections.
Cytohesins are guanine nucleotide exchange factor for ARF-GTPases which regulate important aspects of vesicle transport in cells, but are also involved in the signal transduction of important cell surface receptors, e.g. integrins and the insulin receptor. In the course of this project we will employ knock-out models for the cytohesins to unravel their roles in the innate immune response againt bacteria such as legionella, which reside in intracellular, vesicular compartments.
Dept. of Microbiology and Immunology
Our joint project aims at harnessing a recently discovered immune cell type, the mucosa-associated invariant T (MAIT) cells, to improve vaccination strategies against mucosal virus infections. It combines the expertise of Christian Kurts on antigen cross-presentation with that of Dale Godfrey on innate lymphocyte subsets. The PhD project encompasses basic scientific questions regarding immune regulation, immune cell migration and cell biology and translational question in human immunology.
Dept. of Microbiology and Immunology
In order to avoid complete organ destruction, it is important to understand immune-suppressive mechanisms that arise in non-lymphoid tissues during acute and chronic inflammation. Such immune regulation can stem from suppressive lymphocyte populations such as regulatory T cells or myeloid cell subsets (e.g. DC or MDSCs). In this project we are analyzing and identifying the molecular regulators that control the transcriptional and metabolic profiles of these suppressive immune populations in the inflamed tissues of kidney, lung and skin.
This project aims to unravel novel pathways and mechanisms of cell-cell communication in immunological complex tissues by single-cell RNA sequencing and computational modelling. These interaction models will be tested in a murine influenza model.
Malignant melanoma is highly aggressive skin cancer and a paradigm disease for the development of novel immunotherapeutic strategies. In this project we aim to determine the role of permanently tissue–resident cytotoxic T memory (TRM) cells in melanoma growth surveillance. We also analyze the reciprocal interactions between melanoma cells and melanoma–specific TRM cells. The findings will improve our understanding how melanoma cells and the immune system could be re-educated to improve current treatments.
Aim of this project is to investigate the influence of neuroinflammation on amyloid beta production, the impact of immunostimulated microglia supernatants on BACE1 and APP trafficking and amyloid beta production in primary neurons.
NLRP1 was the first NLR protein described to form an inflammasome, recruiting ASC to activate Caspase-1, which processes interleukin-1β and interleukin-18. In this joined project, we aim at defining the genetic and structural information that regulates this innate immune sensor. Autolytic cleavage within the FIIND domain of NLRP1 has been implicated in activation, and common variants near this region are susceptibility loci for a broad range of autoimmune diseases. The familial loss of function mutations in the N-terminal pyrin domain highlight that this autolytic cleavage is indeed a pre-requisite for NLRP1 activation, liberating a C-terminal fragment containing a CARD domain to form an ASC dependent inflammasome. We want to determine the structural and functional basis of this NLRP1 regulation mechanisms.
The aim of the project is to evaluate nucleic acid recognition based signaling pathways in resting or activated T cells and if presence of HIV-1 impair or mutate such pathways of the innate immune system in persistently infected T cells.