Our research
The group's research aims to understand how the tissue microenvironment influences immune cell responses and immune-mediated pathology. A special focus is on the ability of tissue-specific cells to shape the function of myeloid cells in bacterial infections as well as chronic inflammatory conditions.
We use the latest technology and take advantage of our latest advances in the development of immunocompetent organotypic tissues. They mimic specific tissues optimized for the study of infections at specific sites, e.g. lung and skin. The goal is identifying new biomarkers for precision diagnostics and improved prognosis, as well as implementing new tailored therapeutic strategies.
Key focus of the research
A key focus of the group's research is to gain insights how the tissue microenvironment influences immune cell responses and immune-mediated pathology. A special focus is on the ability of tissue-specific cells, such as fibroblasts, to shape the function of myeloid immune cells in bacterial infections as well as chronic inflammatory conditions.
The goals are to:
- Develop customized human organotypic models for disease mechanism identification, biomarker detection, and validation of interventions in sever bacterial infectious diseases
- Utilize identified disease mechanisms to develop tailored therapy and implement personalized medicine in sever infectious diseases.
- Identify central host-derived mediators which in the tissue environment drives bacteria behavior and characteristics, such as biofilm formation and persistence.
Of particular interest are the two Gram-positive bacteria Streptococcus pyogenes and Staphylococcus aureus. Both of these Gram-positive bacteria, may cause highly aggressive invasive infections such as toxic shock, necrotizing pneumonia and necrotizing fasciitis that are associated with substantial morbidity and mortality.
Contributing to local immune responses and pathology
Studying the many processes involved in shaping inflammatory responses and pathogenesis at the tissue site in human infectious diseases are difficult. Developing and using human multicellular three-dimensional (3D) tissue models, so called organotypic models, with myeloid immune cells and that mimic real tissues, provides unique tools to study host-pathogen interactions. This means contributing to local immune responses and pathology.
Keywords
Infection, inflammation, myeloid immune cells, human organotypic models, personalized medicine
Open positions
We always want to get in touch with talented potential co-workers. If you are interested in doing research within our group, as a degree project or as a researcher, please contact the Group leader: mattias.svensson@ki.se
Collaborations
Sweden
Anna Norrby-Teglund, Professor in medical microbial pathogenesis, Karolinska Institutet, Coordinator of the INFECT, PerAID and PerMIT projects
Kristoffer Strålin, MD, PhD, Associate Professor. Specialist in Infectious Diseases, Karolinska University Hospital
Teresa Frisan, Professor in Cell and Molecular Biology at Umeå University
International
- Steinar Skrede, University of Bergen, Norway
- Ole Hyldegaard, Rigshospitalet and University of Copenhagen, Denmark
- Edoardo Saccenti, Wageningen University and Research, the Netherlands
- Vitor Martin dos Santos, WUR and LifeGlimmer, Berlin, Germany
- Jan-Kristian Damås and Erik Solligård, St Olav’s Hospital and NTNU, Trondheim, Norway
- Annebeth de Vries, Red Cross, the Netherlands
- Suba Nookala, University of North Dakota, USA
- Annelies Zinkernagel, University of Zürich, Switzerland
Recent and ongoing projects
INFECT-project, 2013-2018
Supported by FP7 Health
The INFECT-project included 14 partners from across Europe, Israel and the US. The overall goal of the project was to advance our understanding of the pathophysiological mechanisms, prognosis, and diagnosis of the multifactorial highly lethal necrotizing soft tissue infections (NSTIs). NSTI’s are rapidly spreading infections that may cause extensive soft tissue or limb loss, multiorgan failure and are associated with a considerable fatality rate.
There is an urgent need for novel diagnostic and therapeutic strategies in order to improve outcome of NSTIs. To achieve this, a comprehensive and integrated knowledge of diagnostic features, causative microbial agent, treatment strategies, and pathogenic mechanisms (host and bacterial disease traits and their underlying interaction network) was sought. INFECT obtained such insights through an integrated systems biology approach in patients and different clinically relevant experimental models. A key achievement of INFECT was the enrollment of NSTI patients and the creation of the world’s largest patient cohort and associated biobank. Analyses of the comprehensive clinical registry generated an advanced understanding of these patients and underlying disease mechanisms.
Personalized Medicine in Infectious Diseases
The INFECT clinical registry and biobank now offer a resource for recently started multinational projects, PerAID and PERMIT. These projects build on the advances made through the systems medicine approach to achieve personalized medicine in infectious diseases. The two projects are ambitious covering both severe soft tissue infections and the large heterogeneous group of sepsis. Activities range from the establishment of a Nordic platform for personalized medicine in infections, to translational research aimed to identify disease signatures and biomarkers that can be used for individualized therapy. Another activity is the development of clinical decision support tools.
Unravelling tissue-specific pathways controlling human monocyte and neutrophil functions in response to bacterial toxins
This project focuses on elucidating mechanisms by which pore-forming toxins contribute to staphylococcal pneumonia through immunomodulatory activities in the lung. Specifically, we will use our unique human organotypic lung model, combined with human monocytes and neutrophils, and samples from S. aureus infected patients. Technologies used include: multicolor confocal and flow cytometry, single cell gene expression, metabolomics and protein profiling. These studies will contribute to detect mechanisms underlying S. aureus-mediated immunomodulation in lung tissue and identify risk factors to develop severe pneumonia. Long-term this forms the basis to develop new diagnostic and treatment strategies, and the identification of toxin-induced responses may also be exploited to treat other serious lung diseases.